mobic and Pain

Although laboratory animals experience pain as a necessary component of the objectives of experimental protocols, the level of pain should be minimized through use of an adequate analgesic regimen. The non-steroidal anti-inflammatory drug meloxicam may be beneficial in alleviating post-operative pain in mice, although no regimen has been demonstrated as universally efficacious owing to differences in experimental protocols, strain, sex, and incomplete descriptions of methodology in the literature. The aim of this systematic literature review was to identify potential applications of meloxicam for pain management in experimental mice and to evaluate the general quality of study design. Searches of MEDLINE, Scopus and CAB Direct databases elicited 94 articles published between January 2000 and April 2020 that focused on the analgesic efficacy of meloxicam in the management of momentary or persistent pain in mice. The extracted data showed that most articles were deficient in descriptions of housing, husbandry, group size calculation and humane endpoint criteria, while few described adverse effects of the drug. A wide range of dosages of meloxicam was identified with analgesic efficiencies that varied considerably according to the different models or procedures studied. It was impossible to correlate the extracted data into a single meta-analysis because of the differences in experimental protocols and strains employed, the low representation of female mice in the studies, and incomplete descriptions of the methodology applied. We conclude that meloxicam has potential application for pain management in mice but that the dosage must be adjusted carefully according to the experimental procedures. Moreover, authors must take more care in designing their studies and in describing the methodology employed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Meloxicam; Mice; Pain

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial effects of NSAIDs in children and adolescents, there is a lack of comprehensive data in infants. The present review summarizes the current knowledge on the safety and efficacy of various NSAIDs used in infants for which data are available, and includes ibuprofen, dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin, niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid, and nimesulide. The efficacy of NSAIDs has been documented for a variety of conditions, such as fever and pain. NSAIDs are also the main pillars of anti-inflammatory treatment, such as in pediatric inflammatory rheumatic diseases. Limited data are available on the safety of most NSAIDs in infants. Adverse drug reactions may be renal, gastrointestinal, hematological, or immunologic. Since NSAIDs are among the most frequently used drugs in the pediatric population, safety and efficacy studies can be performed as part of normal clinical routine, even in young infants. Available data sources, such as (electronic) medical records, should be used for safety and efficacy analyses. On a larger scale, existing data sources, e.g. adverse drug reaction programs/networks, spontaneous national reporting systems, and electronic medical records should be assessed with child-specific methods in order to detect safety signals pertinent to certain pediatric age groups or disease entities. To improve the safety of NSAIDs in infants, treatment needs to be initiated with the lowest age-appropriate or weight-based dose. Duration of treatment and amount of drug used should be regularly evaluated and maximum dose limits and other recommendations by the manufacturer or expert committees should be followed. Treatment for non-chronic conditions such as fever and acute (postoperative) pain should be kept as short as possible. Patients with chronic conditions should be regularly monitored for possible adverse effects of NSAIDs.

Topics: Adolescent; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Celecoxib; Child; Chronic Disease; Diclofenac; Flurbiprofen; Humans; Ibuprofen; Infant; Ketoprofen; Ketorolac; Meloxicam; Naproxen; Niflumic Acid; Pain

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Drug Interactions; Female; Humans; Male; Meloxicam; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Thiazines; Thiazoles

BestBETs for Vets are generated by the Centre for Evidence-based Veterinary Medicine at the University of Nottingham to help answer specific questions and assist in clinical decision making. Although evidence is often limited, they aim to find, present and draw conclusions from the best available evidence, using a standardised framework. A more detailed description of how BestBETs for Vets are produced was published in a previous issue of Veterinary Record (VR, April 4, 2015, pp 354-356).

Topics: Animals; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Meloxicam; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Thiazines; Thiazoles

Over the past decade, there have been several nonsteroidal anti-inflammatory drugs (NSAIDS) introduced in veterinary medicine with an increased gastrointestinal safety profile consistent with a cyclooxygenase (COX)-1-sparing effect. More recently, an NSAID with additional 5-lipoxygenase (5-LOX) activity has also been approved for use. Although it is tempting to equate in vitro COX-2/COX-1 and 5-LOX inhibition to overall in vivo safety, the data do not support this approach. The true overall safety for any individual compound is based on its evaluation in laboratory margin-of-safety studies, reproductive safety studies, and blind multicenter field studies in client-owned animals. Therefore, when choosing a COX-2-selective or dual-inhibitor NSAID for clinical use, all in vivo data must be taken into account to understand comparative safety, and continued use must be based on the drug's performance in the individual being treated. Until head-to-head trials in multicenter blind studies are published, comments on comparative safety and effectiveness must be reserved.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cats; Cyclooxygenase 2 Inhibitors; Dogs; Etodolac; Meloxicam; Pain; Pain Measurement; Pyrazoles; Sulfones; Thiazines; Thiazoles

To analyze selective COX 2 inhibitor nonsteroidal anti-inflammatory drugs (NSAID) in terms of their mechanism of action, principal indications, posology and most common adverse effects.. MEDLINE and LILACS databases and Food and Drug Administration (FDA) and National Agency for Sanitary Vigilance (ANVISA - Agência Nacional de Vigilância Sanitária) websites. The most important articles were selected and preference was given to articles published within the last 5 years.. The principal indications for NSAID are for control of pain and acute and chronic inflammation. There is no overwhelming evidence that demonstrates the superiority of one NSAID over another in terms of effectiveness. To date none of the COX 2 inhibitors has been liberated for use in the pediatric age group. Only meloxicam and etoricoxib can be prescribed for adolescents (13 and 16 years, respectively). Selective COX 2 inhibitors are indicated for patients with adverse effects that have proven to be associated with nonselective NSAID use. Selective COX 2 inhibitors can be prescribed in some cases of allergy to aspirin, but they must be used with care. Principal adverse effects include cardiovascular events and thrombotic phenomena.. Selective COX 2 inhibitors are medicines that have been used in certain well-defined clinical situations and which may offer certain advantages over nonselective NSAID. Nevertheless, taking into consideration the higher cost involved and the potential for adverse cardiovascular effects, they should be employed only in accordance with strict criteria.

Topics: Adolescent; Aspirin; Celecoxib; Child; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drug Interactions; Etoricoxib; Fever; Humans; Hypersensitivity, Immediate; Inflammation; Leukotrienes; Meloxicam; Naproxen; Pain; Prostaglandins; Pyrazoles; Pyridines; Sulfonamides; Sulfones; Thiazines; Thiazoles; Treatment Outcome

Meloxicam (Mobic trade mark, Boehringer Ingelheim) is a relatively new oral non-steroidal anti-inflammatory drug (NSAID) approved for the treatment of osteoarthritis in the US. It has also been evaluated for the treatment of rheumatoid arthritis, ankylosing spondylitis and acute 'rheumatic' pain. Meloxicam has been shown to be COX-2 preferential, particularly at its lowest therapeutic dose, and is anti-inflammatory by inhibiting prostanoid synthesis in inflammatory cells. Since it is COX-2 preferential, it would be expected to have less gastrointestinal toxicity than non-selective NSAIDs. In clinical trials of meloxicam in osteoarthritis, it was found to be as effective as piroxicam, diclofenac and naproxen with less clinical gastrointestinal symptoms and less perforations, obstructions and bleeds by meta-analysis. Adverse events, including peripheral oedema and hypertension, occurred at a similar rate as with traditional NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Interactions; Humans; Meloxicam; Osteoarthritis; Pain; Product Surveillance, Postmarketing; Spondylitis, Ankylosing; Thiazines; Thiazoles

Meloxicam (Mobic) is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid, exhibiting selectivity for cyclooxygenase (COX)-2 over COX-1. Meloxicam has shown potent anti-inflammatory and analgesic activity together with low gastrointestinal toxicity in animal models. It is a potent inhibitor not only of acute exudation in adjuvant arthritis in the rat, but also of bone and cartilage destruction. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of other NSAIDs. Meloxicam in therapeutic doses was found to have no effect on bleeding time or platelet aggregation in healthy volunteers. In clinical studies, meloxicam has shown reliable efficacy against rheumatoid arthritis, osteoarthritis, lumbago (low back pain), scapulohumeral periarthritis, and neck-shoulder-arm syndrome with low gastrointestinal toxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase 2; Enzyme Inhibitors; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Inflammation; Isoenzymes; Meloxicam; Membrane Proteins; Pain; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Rats; Thiazines; Thiazoles

Topics: Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Isoenzymes; Lactones; Meloxicam; Membrane Proteins; Pain; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides; Sulfones; Thiazines; Thiazoles

Most studies of nonsteroidal anti-inflammatory drugs (NSAID) do not demonstrate appreciable differences in efficacy. As awareness of the adverse effects associated with NSAID use increases, safety is becoming the primary concern among physicians when selecting NSAID for use by their human patients. However, veterinarians may be less aware of the safety concerns associated with NSAID use. A wide range of NSAID is used to treat human beings with osteoarthrits; however, it is imperative to remember that dogs are especially sensitive to these drugs, and reports of serious, and occasionally fatal, complications are numerous. Carprofen is a propionic acid-derived NSAID that has anti-inflammatory, analgesic, and antipyretic activity. In animals, carprofen is as potent as indomethacina and more potent than aspirin or phenlbutazone, but carprofen appears to be safer than most other NSAID.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carbazoles; Clonixin; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Ibuprofen; Indomethacin; Ketoprofen; Meclofenamic Acid; Meloxicam; Naproxen; Osteoarthritis; Pain; Phenylbutazone; Piroxicam; Thiazines; Thiazoles

The aim of this prospective, double-blind, randomized controlled trial was to compare the effect of oral premedication of meloxicam, ketorolac, dexamethasone, ibuprofen, or placebo on the success of inferior alveolar nerve blocks (IANB) of mandibular posterior teeth in patients experiencing symptomatic irreversible pulpitis.. Two hundred and fifty emergency patients in moderate to severe pain diagnosed with symptomatic irreversible pulpitis of a mandibular first or second molar randomly received, in a double-blind manner, identical capsules containing either meloxicam 7.5 mg, ketorolac 10 mg, dexamethasone 0.5 mg, ibuprofen 600 mg, or placebo 60 minutes before the administration of an IANB. Profound lip numbness was assessed after 15 minutes. Access cavities were then prepared and success of IANB was defined as no or mild pain (Heft-Parker visual analog scale recordings) during access preparation and root canal instrumentation. The data were analyzed using chi-square and Kruskal-Wallis tests.. The overall success rates for the meloxicam 7.5 mg, ketorolac 10 mg, dexamethasone 0.5 mg, and ibuprofen 600 mg groups were 52%, 64%, 54%, and 58%, respectively, with no significant differences in success rates among the premedications groups (P > .05). However, the tested premedications revealed significant differences compared with the placebo group (32% success rate) (P < .05).. Premedication with meloxicam, ketorolac, dexamethasone, and ibuprofen increased the efficacy of IANB in mandibular molars with symptomatic irreversible pulpitis. (Quintessence Int 2023;54:92-99; doi: 10.3290/j.qi.b3605097).

Topics: Anesthesia, Dental; Anesthetics, Local; Dexamethasone; Double-Blind Method; Humans; Ibuprofen; Ketorolac; Lidocaine; Mandibular Nerve; Meloxicam; Nerve Block; Pain; Premedication; Prospective Studies; Pulpitis

This randomised, prospective, masked clinical trial evaluated the postoperative analgesic efficacy of an ultrasound-guided transversus abdominis plane block (TAPB) with bupivacaine in cats undergoing ovariohysterectomy.. Thirty-two healthy adult female cats undergoing elective ovariohysterectomy were randomised to undergo TAPB with bupivacaine (treatment group [TG], n = 16) vs placebo (control group [CG], n = 16) in addition to preoperative analgesia with buprenorphine (0.02 mg/kg IM). All patients received a general anaesthetic and, before surgical incision, a bilateral two-point (subcostal and lateral-longitudinal) TAPB was performed using 1 ml/kg bupivacaine 0.25% (0.25 ml/kg/point) or saline. Each cat was assessed by a blinded investigator before premedication (0 h) and at 1, 2, 3, 4, 8, 10 and 24 h postoperatively using the UNESP-Botucatu Feline Pain Scale - short form. Buprenorphine (0.02 mg/kg IV) and meloxicam (0.2 mg/kg SC) were administered when pain scores were ⩾4/12. Ten hours postoperatively, meloxicam was administered to cats that did not receive rescue analgesia. Statistical analysis included Student's. Of the 32 cats enrolled, three in the CG were excluded from the analysis. The prevalence of rescue analgesia was significantly higher in the CG (n = 13/13) than in the TG (n = 3/16;. A bilateral ultrasound-guided two-point TAPB with bupivacaine in combination with systemic buprenorphine provided superior postoperative analgesia than buprenorphine alone in cats undergoing ovariohysterectomy.

Topics: Abdominal Muscles; Analgesics; Animals; Bupivacaine; Buprenorphine; Cats; Female; Meloxicam; Pain; Prospective Studies; Ultrasonography, Interventional

Caustic paste disbudding (CPD) is widely utilized for calves, which has been known to result in adverse effects on the calves and ethical concerns related to animal welfare, despite the use of local anesthetics. The administration of meloxicam has been demonstrated to provide benefits in alleviating pain and inflammation in juvenile calves under 9 d old and subjected to CPD. Nonetheless, there is a scarcity of literature documenting the beneficial impact of meloxicam in alleviating pain in calves aged over 9 d that have undergone CPD. Therefore, the objective of this clinical trial was to evaluate the efficacy of administering meloxicam and lidocaine for cornual nerve block together in mitigating the deleterious effects of CPD, as opposed to using lidocaine alone in calves older than 9 d. Thirty Holstein calves, aged between 10 and 21 d, were enrolled and randomly assigned to 1 of 2 treatments: lidocaine alone (Placebo), lidocaine and normal saline treatment before CPD, and lidocaine plus meloxicam, lidocaine and 0.5 mg/kg of meloxicam treatment prior to CPD. The researchers were blind to the treatment of calves to control the subjective error. The occurrences of actions associated with pain, which included head shaking, head rubbing, ear flicking, tail flicking, kicking, and head passing through the fence, were recorded. Physiological performance, including the respiration rate, heart rate, rectal temperature, mechanical nociceptive threshold (MNT), food intake, and daily activity level, was monitored. Hematological conditions were ascertained through the use of routine blood tests and enzyme-linked immunosorbent assay. The generalized linear mixed model was employed to analyze the data. The research findings revealed that applying the CPD procedure significantly elevated the frequencies of tail flicking, head shaking, and kicking, resulted in increases in respiratory rate, heart rate, daily active steps, and food intake and a decrease in MNT, and led to alterations in hematological markers, including platelet counts, mean platelet volume, prostaglandin E2, constitutive nitric oxide synthase, and hydroxyl radical. Considerable benefits, such as lower heart rates, higher food intake, and MNTs, as well as lower levels of white blood cell counts, lymphocyte counts, hemoglobin, mean platelet volume, prostaglandin E2, tumor necrosis factor-α, constitutive nitric oxide synthase, malondialdehyde, and hydroxyl radical, were observed in the calves that received m. Caustic paste disbudding (CPD) is a widely used practice in the cattle industry, yet there is a shortage of literature on the effects of meloxicam on calves aged 10 to 21 d who have undergone this procedure. In this clinical trial, we conducted a comparative analysis of the pain-related behavioral, physiological, and hematological performance of calves that were administered with either lidocaine plus normal saline (n = 15) or lidocaine plus meloxicam (n = 15) before undergoing disbudding operations. The findings demonstrated that the CPD operation had a significant impact on the pain-related behavior, physiological functions, and serum anti-inflammatory and antioxidative markers of the calves. On the other hand, the administration of meloxicam had notable advantages for the calves by enhancing the physiological and hematological parameters.

Topics: Animal Welfare; Animals; Cattle; Caustics; Dinoprostone; Horns; Hydroxyl Radical; Inflammation; Lidocaine; Meloxicam; Pain

Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects.. The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg Mobic. QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain.. The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).

Topics: Area Under Curve; Cross-Over Studies; Dose-Response Relationship, Drug; East Asian People; Healthy Volunteers; Humans; Meloxicam; Pain

Extended-release (ER) local anesthetics can be used in multi-modal analgesia or in situations in which systemic analgesics may alter animal physiology and thus introduce interpretational confounds. In this study, we compared the analgesic efficacy of an ER buprenorphine formulation with that of a synergistic combination of ER bupivacaine and meloxicam. Female and male CD1 mice were randomly assigned to receive subcutaneous buprenorphine (3.25mg/kg) preemptively, subcutaneous infiltration of bupivacaine???meloxicam (0.03mL at incision closure (bupivacaine, 35mg/kg; meloxicam, 1mg/kg), or saline (10mL/kg SC) after induction of anesthesia. After laparotomy, mice were assessed for changes in daily body weight, rearing frequency, nest consolidation scores, time-to-integrate-nest test (TINT), and response to von Frey testing at 4, 8, 24, 48, and 72h after surgery. Daily weight, nest consolidation scores and rearing frequency were not significantly different among the 3 groups. TINT had fallen significantly response at 24 and 48h after injection in the ER buprenorphine group as compared with the saline and ER bupivacaine-meloxicam groups. Nociceptive thresholds, as assessed with von Frey testing, differed between saline controls and both analgesic groups at 4, 8, 24, 48, and 72 h after surgery. None of the mice in the bupivacaine???meloxicam group developed signs of neurotoxicity, a potential side effect of high-dose local anesthetics. This study demonstrates that local ER bupivacaine???meloxicam may be a useful alternative to systemic, ER buprenorphine for the relief of pain after laparotomy in mice.

Topics: Analgesics; Analgesics, Opioid; Anesthetics, Local; Animals; Bupivacaine; Buprenorphine; Female; Laparotomy; Male; Meloxicam; Mice; Pain; Pain, Postoperative; Rodent Diseases

Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of low dose meloxicam. Toceranib phosphate is used to treat several feline cancers and is well tolerated. This study aimed to determine the tolerability and adverse event profile of combined toceranib and low dose meloxicam in cancer-bearing cats. Secondary goals involved assessing anticancer tumor efficacy and impact upon quality of life and analgesia.. Cats with any cancer not involving the kidneys were eligible. The study adopted a conventional 3 + 3 dose escalation design. Toceranib was administered every other day at a standard dose with meloxicam administered in an escalating fashion in subsequent cohorts, at a starting dose of 0.01 mg/kg on opposite days to toceranib, up to a maximum of 0.02 mg/kg daily, based upon previous safety studies. Laboratory work, blood pressure, tumor measurements, pain score and client-completed quality-of-life surveys were recorded every 2-4 weeks during the 12-week study period.. Twenty-one cats were enrolled. When combined with toceranib, a meloxicam dose of 0.02 mg/kg q24h was safe and well tolerated, with no cats being withdrawn due to adverse events from the drug combination. The majority of cats demonstrated clinical benefit with stable to mildly improved tumor measurements, quality of life and pain scores.. Low dose meloxicam combined with toceranib is safe and well tolerated in cancer-bearing cats. Continued patient recruitment and data collection are needed to determine the maximum tolerated dose of meloxicam. The results of our study will guide further phase II/III trials.

Topics: Animals; Cat Diseases; Cats; Meloxicam; Neoplasms; Pain; Quality of Life

Hot-iron branding uses thermal injury to permanently identify cattle causing painful tissue damage. The primary objective was to examine the physiological and behavioral effects of oral meloxicam (MEL), compared to a control, administered at the time of hot-iron branding in Angus and Hereford steers and heifers. The secondary objectives were to investigate breed and sex effects on pain biomarkers. A total of 70 yearlings, consisting of 35 heifers and 35 steers (Angus, Hereford, or Angus × Hereford), were enrolled in the study. Animals were blocked by sex, randomized across weight, and assigned to receive MEL (1 mg/kg) or a placebo (CON). Biomarkers were assessed for 48 h after branding and included infrared thermography (IRT), mechanical nociceptive threshold (MNT), accelerometry and a visual analog scale (VAS), and serum cortisol and prostaglandin E2 metabolites (PGEM). Wound healing was assessed for 12 wk. Hair samples to quantify cortisol levels were taken prior to and 30 d post-branding. Responses were analyzed using repeated measures with calf nested in treatment as a random effect, and treatment, time, treatment by time interaction, breed, and sex as fixed effects. There was a treatment by time interaction for PGEM (P < 0.01) with MEL having lower values than CON at 6, 24, and 48 h (MEL: 18.34 ± 3.52, 19.61 ± 3.48, and 22.24 ± 3.48 pg/mL, respectively; CON: 32.57 ± 3.58, 37.00 ± 3.52, and 33.07 ± 3.48 pg/mL; P < 0.01). MEL showed less of a difference in maximum IRT values between the branded (2.27 ± 0.29 °C) and control site (3.15 ± 0.29 °C; P < 0.01). MEL took fewer lying bouts at 0-12 h (4.91 bouts ± 0.56) compared with CON (6.87 bouts ± 0.55; P < 0.01). Compared with Hereford calves, Angus calves exhibited greater serum but lower hair cortisol, greater PGEM, more lying bouts, and less healed wound scores at 3, 4, and 5 wk. Compared with heifers, steers exhibited lower PGEM, lower branding site and ocular IRT, higher MNT, and lower plasma meloxicam levels. Steers spent more time lying, took more lying bouts and had greater VAS pain, and more healed wound scores at 5 wk than heifers. Meloxicam administration at branding reduced branding and control site temperature differences and reduced lying bouts for the first 12 h. Breed and sex effects were observed across many biomarkers. Changes from baseline values for IRT, MNT, lying time, step count, VAS pain, and wound scoring all support that branding cattle is painful.. Hot-iron branding uses thermal injury to permanently identify cattle causing painful tissue damage. The primary objective was to examine the effects of oral meloxicam (MEL), compared with a control, administered at the time of hot-iron branding in Angus and Hereford steers and heifers. The secondary objectives were to investigate breed and sex effects on pain biomarkers. A total of 70 yearlings, consisting of 35 heifers and 35 steers (Angus, Hereford, or Angus × Hereford), were enrolled. Animals were assigned to receive MEL or a placebo. Changes from baseline values for infrared thermography (IRT), mechanical nociceptive threshold, lying time, step count, visual analog scale score, and wound scoring all support that hot-iron branding cattle is painful and investigation into analgesic strategies is needed. MEL administration reduced IRT differences from the branding and control site and reduced lying bouts. Breed and sex effects were observed across a wide range of biomarkers and should be considered in future pain studies. The practicality of administering a nonsteroidal anti-inflammatory drug once at the time of branding is attractive. However, a multimodal approach using a combination of analgesics or longer acting analgesic option warrants further investigation to alleviate pain and discomfort caused by hot-iron branding.

Topics: Animals; Biomarkers; Cattle; Female; Iron; Meloxicam; Pain; Pain Measurement

The objective of this study was to determine the effects of flunixin meglumine or meloxicam on behavioral response and performance characteristics associated with surgical castration in crossbred bulls. Intact male Bos taurus calves (n = 252; averaging 176 kg) were randomly allocated into one of three treatment groups within pen: control (CON), flunixin meglumine (FLU; 2.2 mg/kg intravenous injection), or meloxicam (MEL; 2.0 mg/kg per os). The individual animal was the experimental unit. Calves were individually weighed on days 0 and 14 of the trial to evaluate performance outcomes. On study day 0, treatments were administered, according to their random allocation, immediately prior to surgical castration using the Henderson tool method. Visual analog scale (VAS) assessment and categorical attitude score (CAS) were collected on days -1, 0 (6 h post-castration), 1, 2, 3, and 4 in the study. The VAS was assigned using a 100 mm horizontal line with "normal" labeled at one end of the line and "moribund" at the other end of the horizontal line. The masked observer assigned a mark on the horizontal line based upon the observed severity of pain exhibited by that individual animal. The CAS was assigned by the same observer using five different categories with a score of 0 being "normal". Average daily gain tended (P = 0.09) to be associated with the treatment group, and MEL had a greater (P = 0.04) average daily gain through day 14 compared with CON. A significant (P < 0.01) treatment by day interaction was indicated for VAS score, and MEL had lower VAS scores on days 0, 1, 2, and 3 post-castration compared with CON; FLU had lower VAS scores on days 0 and 1 compared with CON. A significant treatment by day interaction was not present (P = 0.25) for CAS. The FLU had lesser percent CAS ≥1 (17.5%; P = 0.05) compared with CON (29.4%); MEL has lesser percent CAS ≥1 observations (14.9%; P = 0.01) compared with CON. The median VAS increased as CAS was more severe. Results indicated MEL and FLU calves temporally improved behavioral responses following surgical castration with positive numerical trends for a 14 d average daily gain (ADG). The VAS system appeared to be an effective method of subjective evaluation of pain in beef calves in this study. Route of administration, duration of therapy, and low relative cost make oral meloxicam a reasonable analgesic treatment in calves when administered at the time of surgical castration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Clonixin; Male; Meloxicam; Orchiectomy; Pain

To observe the effect of warm acupuncture combined with meloxicam and comprehensive nursing on pain improvement and joint function in patients with knee osteoarthritis.. Eighty-one patients with KOA were randomly divided into control group (CG), traditional Chinese medicine group (TCMG), and combined group (JG). The CG was treated with meloxicam. The TCMG received warm acupuncture treatment. The JG was treated with meloxicam combined with warm acupuncture. Three groups were given comprehensive nursing intervention, and the course of treatment was 4 weeks. Knee function was assessed by knee pain, activity, stability, walking ability, and ability to walk up and down stairs. Improvement time of clinical symptoms of patients was assessed from knee pain, swelling, and movement limitation. Pain mediators (prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT)) were detected by enzyme-linked immunosorbent assay (ELISA). Oxidative stress indicators (superoxide dismutase (SOD) and malondialdehyde (MDA)) of the enrolled patients were detected by water-soluble tetrazolium-1 (WST-1) and the thiobarbituric acid (TBA) method. The clinical efficacy was assessed by the visual analog scale (VAS) score.. After treatment, the pain scores of the three groups decreased, and the scores of mobility, stability, walking ability, and the ability to walk up and down stairs increased. Compared with the CG and the TCMG, the JG had a greater range of changes in pain, mobility, stability, walking ability, and ability to walk up and down stairs after treatment. After 7 d, 14 d, and 28 d treatment, PGE2, SP, DA, 5-HT, and MDA in the three groups were decreased compared with before treatment, and the decrease in the JG was more obvious than that in the CG and the TCMG. SOD levels in the three groups were increased, and the increase in the JG was more obvious than that in the CG and the TCMG. The total effective rate of the JG (96.30%) was significantly different from that of the CG (77.78%) and the TCMG (81.48%). The improvement time of knee pain, swelling, and movement limitation in the JG was shorter than that in the CG and the TCMG, and the difference in the improvement time of movement limitation in the TCMG was statistically significant.. Warm acupuncture combined with meloxicam and comprehensive nursing can effectively improve knee swelling and pain in patients with KOA, and the mechanism may be related to reducing the content of inflammatory mediators.

Topics: Acupuncture Therapy; Dinoprostone; Humans; Knee Joint; Meloxicam; Osteoarthritis, Knee; Pain; Serotonin; Superoxide Dismutase; Treatment Outcome

The objective of this study was to determine the effect of a biologically normal plane of nutrition compared with a limited plane on the primary outcome wound healing, and one dose of nonsteroidal anti-inflammatory drug (NSAID) compared with 2 on the secondary outcomes: lying behavior, haptoglobin concentrations, and mechanical nociceptive threshold (MNT) in calves disbudded via cautery iron. Eighty female Holstein calves were enrolled at birth, individually housed, and fed via a Calf Rail system (Förster Technik). A 2 × 2 factorial design was used to assess the effect of plane of nutrition and an additional NSAID. Calves were randomly assigned to a biologically normal plane of nutrition (BN; offered up to 15 L/d) or a limited plane (LP; offered up to 6 L/d) and to receive one or 2 doses of meloxicam. All calves received a lidocaine cornual nerve block and a subcutaneous injection of meloxicam 15 min before cautery disbudding at 18 to 25 d of age, and half the calves received an additional injection of meloxicam (0.5 mg/kg) 3 d after disbudding. Tissue type present, wound diameter, and wound depth were evaluated 2 times per week for 7 to 8 wk as measures of wound healing, lying behavior was recorded beginning 1 to 2 wk before disbudding until 7 to 8 wk after as a behavioral indicator of pain, haptoglobin concentrations were measured once per day for 7 d after disbudding, and MNT was evaluated 2 times/wk for 3 wk. Survival analyses were analyzed using Cox regression models (wound healing) and continuous data were analyzed using mixed-effect linear regression models. Only 12% of horn buds were completely healed by 7 to 8 wk after disbudding and 54% had re-epithelized at this time. At any time, wounds from BN calves were more likely to have had re-epithelization occur compared with wounds from LP calves (hazard ratio: 1.93, 95% CI: 1.18-3.14). Wounds from calves that received only one dose of NSAID were more likely to have re-epithelization occur, compared with wounds from calves given 2 doses (hazard ratio: 1.87, 95% CI: 1.15-3.05). Wounds from BN calves had smaller diameters and depths over time beginning on wk 3 compared with LP calves. Wounds from calves that received an additional NSAID had larger diameters and depths over time beginning on wk 4 and 3 respectively, compared with calves that only received one dose of NSAID. Calves that received an extra NSAID tended to be less sensitive 7, 10, and 17 d after disbudding compared with calves that only rece

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cautery; Female; Haptoglobins; Horns; Meloxicam; Pain; Wound Healing

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0-2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2-8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0-24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM differenc

Topics: Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cattle Diseases; Clonixin; Dairying; Female; Injections, Intravenous; Lactation; Lameness, Animal; Meloxicam; Pain

This study aimed to compare the analgesic effect, patients' satisfaction, tolerance and hip-joint function recovery by preoperative meloxicam versus postoperative meloxicam in treating hip osteoarthritis (OA) patients receiving total hip arthroplasty (THA). 132 hip OA patients who underwent THA surgery were allocated into postoperative analgesia (POST) and preoperative analgesia (PRE) groups at a 1:1 ratio. In the PRE group, patients took meloxicam 15 mg at 24 h pre-operation, 7.5 mg at 4 h, 24 h, 48 h and 72 h post-operation; in the POST group, patients received meloxicam 15 mg at 4 h post-operation, then 7.5 mg at 24 h, 48 h and 72 h post-operation. Furthermore, postoperative pain, consumption of patient-controlled analgesia (PCA), overall satisfaction and adverse events were evaluated within 96 h post-operation; meanwhile, Harris hip score was assessed within 6 months post-operation. Pain VAS at rest at 6 h, 12 h, 24 h, and pain VAS at passive movement at 6 h, 12 h were decreased in PRE group compared to POST group. In addition, additional consumption of PCA and the total consumption of PCA were both reduced in PRE group compared to POST group. Additionally, overall satisfaction in PRE group was higher at 24 h, 48 h and 72 h compared to POST group. While Harris hip score was of no difference between POST group and PRE group at M3 or M6. Besides, no difference in adverse events incidence was found between the two groups. In conclusion, preoperative meloxicam achieves better efficacy and similar tolerance compared to postoperative meloxicam in hip OA patients post THA.

Topics: Arthroplasty, Replacement, Hip; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Hip; Pain; Pain Management; Pain Measurement; Pain, Postoperative; Patient Satisfaction; Recovery of Function

To evaluate the efficacy of the non-steroidal anti-inflammatory drug, meloxicam, in alleviating pain and inflammation and on production-related variables in a model of sterile acute inflammation in sheep.. Groups of 12 mature Merino ewes received 0, 0.5, 1.0 or 1.5 mg/kg meloxicam subcutaneously 90 min before injection of 0.1 mL turpentine subcutaneously on the anterior aspect of the proximal phalanx of a forelimb. Pain- and inflammation-related variables were assessed at -18, 3, 6, 9, 12, 24, 48 and 72 h relative to meloxicam administration. Daily feed intake and body weight change 7 days later were also assessed. Pain-related variables measured were weight borne on each forelimb, lameness score, time each forelimb was raised in a 20-s interval and tolerance to a noxious mechanical stimulus. Inflammation-related variables measured were skin temperature, limb circumference, body temperature, plasma haptoglobin concentration and peripheral blood leucocyte parameters.. Meloxicam was effective in improving all pain-related variables. A dose-dependent response was seen between 0 and 1.0 mg/kg, with no additional benefit provided by 1.5 mg/kg. At a dose rate of 1.0 mg/kg, meloxicam improved weight borne on the turpentine-treated limb by 14%, reduced the time the treated limb was held in a non-weight-bearing posture by 46%, reduced the lameness score by 58% and improved tolerance to pressure by 52%. No significant effects of meloxicam on inflammatory variables or appetite were observed.. Using a validated pain model, the data suggested that 1.0 mg/kg meloxicam provided significant analgesic benefits to sheep.

Topics: Administration, Intravenous; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Female; Irritants; Lameness, Animal; Meloxicam; New South Wales; Pain; Pain Measurement; Random Allocation; Sheep; Sheep Diseases; Skin Temperature; Turpentine; Weight-Bearing

The present study aimed to use behavioural measures to assess pain induced by surgical castration of piglets, and evaluate the efficacy of pain-relief medications. In total, 143 male piglets from 29 sows were used. The treatments included: 1) non-castration (NC; n = 28), 2) castration without medication (SC; n = 29), 3) castration with meloxicam injection 0.4 mg/kg i.m. (ME; n = 28), 4) castration with 0.5 ml of 2% lidocaine in each testicle (LA; n = 29), and 5) castration with general inhalation anaesthesia using isoflurane (1.5%) and meloxicam injection (GA; n = 29). Behaviour was monitored continuously for a ten minute period one hour prior to castration (-1 h), as well as immediately (0 h), one hour (1 h), and two hours (2 h) after castration. Behaviour was also monitored twice (08:00 and 20:00) during the following day. Compared to -1 h, castration induced changes in several behavioural measures in SC piglets at 0 h, suggesting that castration was painful. Furthermore, inactive standing or sitting, tail wagging and aggressive behaviour differed between SC and NC piglets at 0 h. ME and LA piglets spent less time standing or sitting inactively, and LA and GA piglets showed more tail wagging than SC piglets at 0 h (P < 0.05 for all). No other behavioural measures differed among the various groups of castrated piglets. In conclusion, the results indicate that surgical castration is indeed painful. However, the efficacy of various pain-relief protocols in piglets shortly after castration was not verified.

Topics: Analgesia; Anesthesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Lidocaine; Male; Meloxicam; Orchiectomy; Pain; Pain Management; Pain Measurement; Swine; Thiazines; Thiazoles

Because human patients with monkeypox virus (MPXV) infection report painful symptoms, it is reasonable to assume that animals infected with MPXV experience some degree of pain. Understanding whether and how analgesics affect MPXV disease progression is crucial when planning in vivo challenge experiments. In the current study, we challenged prairie dogs with a low dose (4 ×10³ pfu) of MPXV and treated with meloxicam (NSAID) or buprenorphine (opioid); control animals did not receive analgesia or received analgesia without MPXV challenge. Subsets of animals from each group were serially euthanized during the course of the study. Disease progression and viral kinetics were similar between groups, but MXPVinfected, meloxicam-treated animals showed increasing trends of morbidity and mortality compared with other groups. Differences between no-analgesia MPXV-infected control animals and MPXV-infected animals treated with buprenorphine were minimal. The findings in the current study allow more informed decisions concerning the use of analgesics during experimental MPXV challenge studies, thereby improving animal welfare. In light of these findings, we have modified our pain scale for this animal model to include the use of buprenorphine for pain relief when warranted after MPXV challenge.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Disease Models, Animal; Female; Meloxicam; Monkeypox virus; Mpox (monkeypox); Pain; Pain Management; Sciuridae

The purpose of this study was to evaluate whether pain-related stress caused by disbudding could be detected using nonlinear measures of heart rate variability (HRV). Twenty-five female Holstein calves (4-7 wk of age) were randomly assigned to 1 of 3 treatments: (1) sham disbud (SHAM; n = 9), (2) disbud with lidocaine-meloxicam pain mitigation (MED; n = 8), or (3) disbud without pain mitigation (NoMED; n = 8). Heart rate variability (sample entropy, percentage determinism, percentage recurrence, or mean length of diagonal lines in a recurrence plot) was recorded on d -1, 0, 1, 3, and 5 relative to the experimental procedure, with disbudding taking place on d 0. The short-term detrended fluctuation analysis scaling exponent was greater in MED calves than in SHAM calves, indicating a greater stress response to the disbudding procedure regardless of pain mitigation. These results indicate that calves in the MED group may have experienced pain-related stress as a result of the disbudding procedure. The remaining nonlinear HRV measures did not differ by treatment. Future research on this topic should address additional potential confounding factors, such as the effect of pain-mitigating drugs on autonomic function or the influence of the autonomic nervous system on wound healing, that may prohibit HRV measurement as an indicator of disbudding pain severity.

Topics: Anesthetics, Local; Animals; Cattle; Female; Heart Rate; Horns; Lidocaine; Meloxicam; Pain; Pain Measurement; Random Allocation

Objective To evaluate the efficacy and safety of adalimumab (ADA) versus hyaluronic acid (HA) by intra-articular injection for moderate to severe knee osteoarthritis. Methods Fifty-six consecutive patients with moderate to severe knee osteoarthritis were randomly allocated to either the ADA group or HA group. On day 0, patients in the ADA group received 10 mg of ADA by intra-articular injection, while those in the HA group received 25 mg of HA. All patients received celecoxib at 200 mg/day for 4 weeks. The pain visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Patient Global Assessment (PGA), and Physician Global Assessment (PhGA) scores were assessed. Results At baseline, the pain VAS, WOMAC, PGA, and PhGA scores were similar between the two groups. The decrease in the pain VAS score, WOMAC pain score, WOMAC physical function score, and WOMAC total score from baseline to week 4 were greater in the ADA than HA group. A greater decrease in the PGA and PhGA scores from baseline to week 4 was noted in the ADA than HA group. No difference in adverse events was observed between the two groups. Conclusion ADA by intra-articular injection was effective and tolerated for moderate to severe knee osteoarthritis.

Topics: Adalimumab; Aged; Antirheumatic Agents; Celecoxib; Diclofenac; Female; Humans; Hyaluronic Acid; Ibuprofen; Injections, Intra-Articular; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Patient Safety; Pilot Projects; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

Up to 25% of ovulating women suffer from primary dysmenorrhea, a condition associated with pain and transient-reduced quality of life, along with greater irritability and impaired sleep. In the present study, we asked whether and if so to what extent melatonin and meloxicam can improve subjective and objective sleep and reduce pain among women with primary dysmenorrhea (PD). To this end, we conducted a double-blind cross-over clinical trial lasting for three menstrual cycles. A total of 14 women (mean age M = 27.5 years) with primary dysmenorrhea took part in the study. At baseline, that is, during the first menstruation, they completed a visual analogue scale to rate pain; sleep continuity was assessed via actigraphs, and overall sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Next, participants were randomly assigned to one of two conditions, either melatonin during the second, and meloxicam during the third menstruation, or meloxicam during the second, and melatonin during the third menstruation. Neither participants nor investigators were aware of participants' study assignment. During the second and third menstruations, the assessments described above were repeated. At baseline, sleep assessed both objectively and subjectively was impaired, and pain was high. Subjective sleep improved and pain decreased during the second and third menstruations irrespective of whether melatonin or meloxicam was administered first or second. Likewise, objective sleep efficiency increased and objective sleep latency shortened. The efficacy of melatonin was superior to that of meloxicam. The present pattern of results suggests that both melatonin and meloxicam are suitable to treat pain and PD-related sleep complaints among women with primary dysmenorrhea.

Topics: Adult; Antioxidants; Cross-Over Studies; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Dysmenorrhea; Female; Humans; Irritable Mood; Melatonin; Meloxicam; Pain; Pilot Projects; Quality of Life; Sleep Wake Disorders; Treatment Outcome; Visual Analog Scale

Pain has a negative impact on life satisfaction (LS). Our primary aims were to compare LS in on-opioid and opioid-naïve spine surgery patients and to evaluate whether surgery affects LS during the first 3 weeks after surgery.. After informed consent 200 patients (99 on-opioid, 101 opioid-naïve; 112 male; aged 23-71 years) having elective spine surgery were enrolled. Their LS was evaluated using a four-item Life Satisfaction Scale (4-20, lower score more satisfied) and pain interference using Brief Pain Inventory (BPI)-questionnaire (0-10, lower score, less interference) before and 21 days after surgery.. At baseline LS was lower in the ON-OPIOID-group, mean LS-score 10.6 (SD 3.9), than that in the OPIOID-NAÏVE-group, 9.3 (3.0) (p = .027). At 3 weeks after surgery LS had increased in both groups compared to baseline (p < .001). However, LS was still lower in the ON-OPIOID-group, 9.1 (3.7) than that in the OPIOID-NAÏVE-group, 7.6 (2.7) (p = .005). Patients with lower LS experienced more pain interference pre- and post-operatively (p < .001). At 3 weeks the pain interference had decreased in both groups, in the ON-OPIOID-group from mean BPI-score 5.1 (2.0) to 3.0 (2.0) (p < .001) and in the OPIOID-NAÏVE-group from 4.0 (2.1) to 2.4 (2.3) (p < .001), but BPI-score was still higher in the ON-OPIOID-group (p = .045).. Life satisfaction increased and pain interference decreased in both groups after spine surgery. However, LS was lower and pain interference was more significant in on-opioid patients than that in opioid-naïve patients.

Topics: Acetaminophen; Adult; Aged; Analgesics, Opioid; Drug Combinations; Elective Surgical Procedures; Female; Humans; Ketoprofen; Male; Meloxicam; Middle Aged; Naltrexone; Oxycodone; Pain; Pain Measurement; Personal Satisfaction; Prospective Studies; Quality of Life; Spine; Surveys and Questionnaires; Tromethamine; Young Adult

Objectives The aim of the study was to investigate the effect of the non-steroidal anti-inflammatory drug meloxicam on the clinical course of obstructive idiopathic cystitis in cats in a placebo-controlled clinical study. Methods Thirty-seven cats with obstructive idiopathic cystitis were enrolled. Cats received supportive treatment and an indwelling transurethral catheter for 48 h. On days 0 and 1, all cats received buprenorphine 0.01 mg/kg subcutaneously every 8 h. On day 1, cats were randomly assigned to the meloxicam (n = 18) or placebo group (n = 19) and received meloxicam (0.1 mg/kg on day 1, 0.05 mg/kg on days 2-5) or placebo orally for five consecutive days. Cats were monitored by repeated physical examinations and urinalysis, and with a 5 day questionnaire filled in by the owners after discharge and a telephone interview 3 months after presentation. Parameters for evaluation of treatment success were the occurrence of recurrent urethral obstruction, results of physical examinations and questionnaires. Results Recurrent urethral obstruction occurred in 4/18 cats (22%) in the meloxicam group and 5/19 cats (26%) in the placebo group ( P = 1.000). General demeanour and pain on abdominal palpation during hospitalisation improved significantly in both groups ( P <0.001). After discharge, with regard to general demeanour, food intake and voiding behaviour, there were no significant differences within or between groups at different time points. Conclusions and relevance Orally administered meloxicam for 5 days did not influence the incidence of recurrent urethral obstruction and the recovery from clinical signs in cats with obstructive feline idiopathic cystitis. The persistence of clinical signs in most of the cats 1 week after initial presentation indicates that symptomatic treatment for a longer period of time is warranted.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Cystitis; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Meloxicam; Ownership; Pain; Pain Measurement; Surveys and Questionnaires; Thiazines; Thiazoles; Treatment Outcome; Urethral Obstruction

Parturation is an intrinsically risky and painful process for both the sow and the piglets that can cause welfare and economic problems. Non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to partially alleviate inflammation and pain after farrowing in sows. NSAIDs effects on piglet mortality and performance show discrepancies and no previous studies have investigated the underlying mechanism. The effects of oral meloxicam treatment to sows on immunoglobulin G (IgG) transfer to piglets around farrowing were investigated. A total of 30 multiparous sows were randomly treated with either oral meloxicam or a mock administration as control group. Treatment was administered as soon as possible at the beginning of the farrowing. A total of 325 piglets were individually weighed at farrowing (day 0) and at weaning (day +21) and piglet mortality was registered during lactation. Four piglets per sow (two piglets suckling from anterior teats and two piglets suckling from posterior teats) were selected for blood sampling at day +1, day +2 and day +20 for IgG analyses. Oral meloxicam treatment to sows significantly increased weight at weaning (mean±SE: 6563±86.3g from oral meloxicam group and 6145±103.2g from control group; P=0.0017) and ADG (mean±SE: 236±3.4g/day from oral meloxicam group and 217±4.5g/day from control group; P<0.001) during lactation, but failed to reduce piglet mortality during lactation (6.7% from oral meloxicam group and 6.8% from control group; P=0.89). IgG levels in piglets from the sows treated with oral meloxicam were significantly higher than the control group at day +1 (mean; median [95% CI] for median=31.9; 31.7 [29.6-33.6] vs. 27.9; 26.8 [25.9-28.3] mg/ml, P=0.0013) and day +2 (27.6; 27.0 [24.8-29.6] vs. 24.5; 24.2 [22.1-25.3] mg/ml, P=0.01). However, at day +20, IgG level in piglet serum was not significantly affected by the treatment (7.6; 7.6 [6.7-8.4] vs. 7.1; 6.9 [6.4-7.3] mg/ml, P=0.59). The administration of meloxicam orally at the beginning of the farrowing in multiparous sows increased the concentration of IgG in serum of piglets and enhanced their pre-weaning growth. Future research is warranted to clearly identify the proximate mechanism behind IgG effect.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Female; Immunity, Maternally-Acquired; Immunoglobulin G; Male; Meloxicam; Pain; Parturition; Pregnancy; Survival Rate; Swine; Thiazines; Thiazoles; Weaning

The objectives of the present study were to compare the cortisol response caused by ear tagging piglets with the distress caused by other known painful husbandry procedures (e.g. castration and tail docking) and to evaluate the effectiveness of analgesia with meloxicam to reduce the cortisol response caused by these procedures. In total, 210 male piglets were randomised to equal numbers (n=30) into one of seven groups: a control group which was only handled (H), an ear tagged group that received no analgesia (ET), an ear tagged group with analgesia (ETM), a castration group with no analgesia (C), a castration group with analgesia (CM), a tail-docked group with no analgesia (TD) and a tail-docked group with analgesia (TDM). The procedures were carried out on day 3 or 4 after farrowing. Five blood samples were taken from each piglet: 30 min before the respective procedure (baseline value), and 30, 60 min, 4 and 7 h after processing, to assess cortisol concentrations. Means as well as the area under the curve (AUC) value were analysed and the effective sizes of the procedures were established. At 7 h after the experimental treatment, cortisol concentrations had returned to base values in all groups. ET evoked a greater cortisol response than H piglets at 30 min (P<0.001) and 60 min (P=0.001). The cortisol response to ET was lower than C at 30 min (P=0.001) but did not differ significantly at the other sample times. The mean cortisol response was similar between ET and TD piglets over all sample times. Taking both intensity and duration of the cortisol response into account (AUC), ET evoked a greater response than TD. Analgesia (ETM) resulted in significantly lower cortisol levels than ET at 30 and 60 min post-procedure. Castration (C) provoked the highest cortisol response of all procedures; a significant analgesic effect (CM) was shown only at 4 h post-procedure. TD resulted in significantly higher cortisol levels than H piglets only at 30 min; analgesia (TDM) significantly reduced the cortisol response at 30 min. We conclude that ear tagging causes a dramatic increase in cortisol levels compared with handling alone in piglets, which suggests that this procedure causes substantial distress. However, further research is needed to confirm these results.

Topics: Analgesia; Animal Husbandry; Animal Identification Systems; Animals; Ear; Hydrocortisone; Male; Meloxicam; Orchiectomy; Pain; Stress, Psychological; Swine; Tail; Thiazines; Thiazoles; Time Factors

To assess the effect of analgesia at disbudding on weight gain and milk intake of dairy calves.. Four disbudding protocols were used on 3- to 6-week-old Friesian-Jersey calves. Farm staff disbudded 101 calves without sedation or local analgesia, of which 51 received 20 mg meloxicam S/C. Veterinary staff disbudded 101 calves with sedation and local analgesia, of which 51 also received 20 mg meloxicam S/C. Calves were weighed before disbudding, 15 and 30 days later, and individual milk consumption was recorded for 11 days. Daily weight gain and milk consumption were analysed using mixed models and ANOVA.. From disbudding (Day 0) to Day 15 farmer-disbudded calves receiving meloxicam grew faster (0.65 kg/day) than calves without meloxicam (0.55 kg/day; p=0.011), but an interaction between operator and meloxicam treatment (p=0.056) meant that meloxicam treatment did not increase growth rates in veterinary-disbudded calves (0.63 vs. 0.64 kg/day; p=0.872). From Days 16-30 there was no significant effect of meloxicam on growth rate, but veterinarian-disbudded calves grew faster (0.76 kg/day) than farmer-disbudded calves (0.66 kg/day; p=0.034). Overall, for the first 30 days after disbudding, if meloxicam was not used', veterinarian-disbudded calves grew faster than farmer-disbudded calves (p=0.002). However if meloxicam was used at disbudding there was no difference in growth rate between veterinarian- and farmer-disbudded calves (p=0.878). Mean cumulative milk consumption for the 11 days after disbudding was greater for calves disbudded by veterinary staff than by farm staff (p<0.001), but there was no effect of meloxicam treatment (p=0.618) and no interaction with operator (p=0.86) on cumulative milk consumption.. Three to 6-week-old dairy calves disbudded by farm staff with no analgesia grew significantly slower over the next 15 days than farmer-disbudded calves given meloxicam, and slower over the next 30 days than veterinarian-disbudded calves given xylazine and lignocaine. However addition of meloxicam to the latter protocol had no effect on growth rate. Milk intake was significantly higher for 11 days for veterinarian- compared with farmer-disbudded calves.. This study adds to the evidence that analgesia during disbudding is beneficial for calf productivity as well as calf welfare.

Topics: Analgesia; Anesthetics, Local; Animal Husbandry; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Eating; Horns; Hypnotics and Sedatives; Lidocaine; Meloxicam; Pain; Thiazines; Thiazoles; Weight Gain; Xylazine

Pain associated with lameness on farm is a negative affective state and has a detrimental impact on individual farm animal welfare. Animal pain can be managed utilizing husbandry tools and through pharmacological approaches. Nonsteroidal anti-inflammatory drugs including meloxicam and flunixin meglumine are compounds used in many species for pain management because they are easy to administer, long lasting, and cost-effective. Assessing an animal's biomechanical parameters using such tools as the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system provides an objective, sensitive, and precise means to detect animals in lame states. The objectives of this study were to determine the efficacy of meloxicam and flunixin meglumine for pain mitigation in lame sows using the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Lameness was induced in 24 mature mixed-parity sows using a chemical synovitis model and compared 3 treatments: meloxicam (1.0 mg/kg per os), flunixin meglumine (2.2 mg/kg intramuscular) and sterile saline (intramuscular). Weight distribution (kg) for each foot was collected twice per second for a total of 5 min for each time point using the embedded microcomputer-based force plate system. Stride time, stride length, maximum pressure, activated sensors, and stance time were collected using 3 quality walks (readings) for each time point using the GAITFour pressure mat gait analysis walkway system. Sows administered flunixin meglumine or meloxicam tolerated more weight on their lame leg compared with saline sows (P < 0.005). Sows administered flunixin meglumine or meloxicam had smaller differences in stance time, maximum pressure, and activated sensors between the sound and lame legs compared with saline-treated sows between 37 and 60 h after lameness induction (P < 0.03). In conclusion, flunixin meglumine and meloxicam administration mitigated pain sensitivity in sows after lameness induction when pain sensitivity was evaluated with the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Analgesic drugs may be a key tool to manage negative pain affective states associated with lameness.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomechanical Phenomena; Clonixin; Female; Foot; Gait; Lameness, Animal; Meloxicam; Microcomputers; Pain; Pregnancy; Pressure; Swine; Swine Diseases; Thiazines; Thiazoles; Weight-Bearing

Pain management and welfare are increasingly prevalent concerns within animal agriculture. Analgesics may alleviate pain and inflammation associated with castration of beef cattle. This study was conducted to elucidate the effects of surgical castration on the acute inflammatory response and immunomodulation and whether concurrent oral administration of meloxicam (1 mg/kg BW) would alter these responses. On d -1, crossbred bull calves ( = 30; initial BW = 227.4 ± 10.3 kg) were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices, placed into individual stanchions, and randomly assigned to 1 of 3 treatments. Treatment application occurred at h 0 and consisted of 1) intact bull calves treated with sham castration (CON), 2) bulls surgically castrated without meloxicam administration (CAS), and 3) bulls surgically castrated with oral meloxicam (1 mg/kg BW) administration (MEL). Blood samples were collected at 0.5-h intervals from h -2 to 4, 1.0-h intervals from h 4 to 8, and 12-h intervals from h 12 to 72. Serum was analyzed for cortisol and haptoglobin (Hp) concentrations using ELISA. Whole blood was analyzed for complete blood counts at -2, 0, 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 h, and RT was recorded in 5-min intervals. Postcastration RT was greatest for MEL (39.04), intermediate for CAS (38.99), and least for CON (38.93°C; ≤ 0.01). Serum cortisol was increased ( < 0.001) for CAS (12.3) and MEL (11.3) compared with CON (6.7 ng/mL) during the postcastration period. At 0.5 and 1.5 h, cortisol concentration was greater in CAS and MEL than CON, whereas at 2 and 2.5 h, cortisol concentration was greatest for CAS, intermediate for MEL, and least for CON (treatment × time, < 0.001). Total white blood cell ( ≤ 0.04), lymphocyte ( ≤ 0.02), and monocyte ( ≤ 0.002) counts were greatest for CAS, intermediate for MEL, and least for CON. Administration of MEL reduced ( ≤ 0.002) eosinophil counts during the postcastration period when compared with CON and CAS. The change in serum Hp, relative to baseline values, was reduced for MEL at 36 ( < 0.01) and 60 h ( ≤ 0.03), and the overall Hp concentration was least for MEL ( < 0.001). Oral administration of meloxicam at the time of castration reduced the acute inflammatory response in castrates, as evidenced by a reduction in Hp and certain leukocyte concentrations; it also caused a delayed increase in RT. Further research is needed to determine if this reduced acute inflammatory response w

Topics: Administration, Oral; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Haptoglobins; Hydrocortisone; Inflammation; Male; Meloxicam; Orchiectomy; Pain; Pain, Postoperative; Thiazines; Thiazoles

This study aims to evaluate and compare the effect of pre-procedural administration of acetaminophen, ibuprofen, and meloxicam in reducing pain after separator placement.. Three hundred twenty-one patients who needed orthodontic treatment and aged above 15 were randomly assigned to one of the three study groups: group A: 650 mg acetaminophen, group B: 400 mg ibuprofen, and group C: 7.5 mg meloxicam. All subjects received a single dose of medication 1 h prior to separator placement. Using visual analog scale, patients recorded their pain perception during rest, fitting posterior teeth together, and chewing at time intervals of immediately, 2, 6, 24, and 48 h after separator placement.. There was no significant difference between acetaminophen, ibuprofen, and meloxicam in post-separator placement pain control when administered 1 h before the procedure. In all the groups, at rest, pain level elevated after separator placement and reached its peak at 24 h and then subsided until 48 h. But during chewing and fitting of the posterior teeth, some of the groups reached a peak in pain at 48 h. No significant difference was found in pain experience between males and females.. Meloxicam can be used as an effective analgesic in orthodontic pain control considering it has less gastric side effects compared to the conventional nonsteroidal anti-inflammatory drugs.. Iranian Registry of Clinical Trials, IRCT2015041821828N1.

Topics: Acetaminophen; Adolescent; Adult; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Dental Occlusion; Double-Blind Method; Female; Follow-Up Studies; Humans; Ibuprofen; Male; Mastication; Meloxicam; Orthodontic Appliances; Pain; Pain Measurement; Pain Perception; Premedication; Prospective Studies; Thiazines; Thiazoles; Young Adult

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as meloxicam are commonly used to treat osteoarthritis (OA) but are associated with potentially serious dose-related adverse events (AEs). SoluMatrix meloxicam has been developed with the goal of enabling effective treatment at low doses. This phase 3 study evaluated the efficacy and safety of low-dose SoluMatrix meloxicam capsules 5 mg and 10 mg administered once daily for 12 weeks in patients with OA-related pain.. This randomized, double-blind study enrolled patients ≥40 years of age with confirmed hip or knee OA (Kellgren-Lawrence grade II-III) who were chronic users of NSAIDs and/or acetaminophen for OA pain and had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale mean scores ≥40 mm. Eligible patients experienced an OA pain flare (defined as a ≥15 mm increase in the WOMAC pain subscale score) following discontinuation of NSAIDs/acetaminophen. Patients were randomized to receive once-daily SoluMatrix meloxicam 5 mg or 10 mg, or placebo for 12 weeks. ClinicalTrials.gov identifier: NCT01787188.. The primary outcome measure was the mean change from baseline in WOMAC pain subscale score at week 12.. Low-dose SoluMatrix meloxicam 5 mg (-36.52 [2.49]; P = 0.0005) and 10 mg (-34.41 [2.68]; P = 0.0059) once-daily treatment significantly reduced the mean (standard error) WOMAC pain subscale score from baseline at week 12 compared with placebo (-25.68 [2.64]). Patients treated with SoluMatrix meloxicam 5 mg or 10 mg reported significantly greater improvements in total WOMAC score and in WOMAC stiffness and function subscale scores at 12 weeks compared with placebo. The most common AEs in the combined low-dose SoluMatrix meloxicam group were headache, diarrhea, nausea, osteoarthritis, and urinary tract infection.. Low-dose SoluMatrix meloxicam may have a potential role as a new therapeutic option for the management of OA-related pain.

Topics: Acetaminophen; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Pain Measurement; Thiazines; Thiazoles; Treatment Outcome

To assess the efficacy of oral transmucosal meloxicam for pain relief in lambs at marking.. A blinded, placebo-controlled, randomised, block design field study of 60 Merino lambs aged 7-10 weeks allocated to placebo and meloxicam treatments and studied in two cohorts of 30. Placebo-treated lambs received 1 mL/10 kg of drug vehicle and meloxicam-treated lambs received 1 mg/kg meloxicam at 10 mg/mL. Treatments were administered into the buccal cavity immediately before knife castration and hot-iron tail docking. Lambs were then released into a grassed paddock (0.34 ha). Time to mother-up was recorded and behaviours were observed every 15 min for 8 h and again for 45 min at 24 h. The sequence in which lambs exited the paddock with their mothers was then recorded. Weight change and wound scores were recorded 4 and 7 days after marking.. Meloxicam did not affect mothering-up. In the 8 h following marking, meloxicam led to a 7-fold reduction (P < 0.001) in combined abnormal behaviours (hunched standing, standing with a stretched posture, walking stiffly). The meloxicam group spent significantly less time in standing postures and tended to spend more time grazing, suckling and in normal lying postures. At 24 h, the meloxicam group spent more time lying and less time standing. There was no effect of treatments on the sequence in which lambs moved into a fresh paddock or on weight change.. The buccal meloxicam formulation provided substantial analgesia to lambs on the day of marking. Slight benefits were evident the following morning.

Topics: Administration, Buccal; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Cohort Studies; Female; Male; Meloxicam; Orchiectomy; Pain; Sheep; Single-Blind Method; Statistics, Nonparametric; Thiazines; Thiazoles; Wound Healing

Parturition is a necessary event for production in dairy cattle, and assistance at calving is common. There is limited use of nonsteroidal antiinflammatory drugs for the alleviation of calving pain and a paucity of research on the effects of these drugs on postpartum health and performance. This randomized triple blind clinical trial involved Holstein cows (n=42) and heifers (n=61) that experienced an assisted parturition. These animals received either 1 injection of meloxicam (0.5mg/kg of body weight) or placebo subcutaneously 24h following calving. Outcome measures included dry matter intake (DMI) and milk production for the first 14d in milk, blood metabolites sampled over 12d, health events for the first 60d in milk, as well as lying and feeding behavior 24h following injection. Continuous data were analyzed using multivariable regression models. Binary outcomes were analyzed using a mixed logistic model with cow modeled using a random intercept. This study failed to show any significant effects of treatment on DMI, milk production, blood metabolites, or health events. A possible explanation for the lack of treatment differences could be that the meloxicam was administered too late after calving. Meloxicam increased feeding time as well as bunk visit frequency in the 24h following injection. Regardless of treatment, animals that had retained fetal membranes produced less milk and had higher serum haptoglobin concentrations. Future research is warranted to examine the effects of antiinflammatory drugs administered closer to the time of calving on health and production.

Topics: 3-Hydroxybutyric Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Weight; Cattle; Cattle Diseases; Dystocia; Eating; Fatty Acids, Nonesterified; Feeding Behavior; Female; Lactation; Meloxicam; Milk; Pain; Parturition; Placebos; Pregnancy; Thiazines; Thiazoles

Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam treatment significantly reduced infarct volume and may be a confounder if used as an analgesic during MCAO surgery. Furthermore, investigation of behavioral profiles by using an automated behavioral scoring system showed that rearing and sniffing behaviors decreased as infarct volume increased. This suggests that studies of exploratory behavior may aid in developing new markers of short-term stroke-related behavioral deficiencies in laboratory mice.

Topics: Analgesics; Animals; Brain Ischemia; Buprenorphine; Corticosterone; Infarction, Middle Cerebral Artery; Male; Meloxicam; Mice; Mice, Inbred C57BL; Pain; Pain Management; Research Design; Thiazines; Thiazoles

Non-steroidal anti-inflammatory drugs (NSAIDs) are used routinely to control pain and inflammation after surgery in dogs. Robenacoxib is a new NSAID with high selectivity for the cyclo-oxygenase (COX)-2 isoform of COX. The objective of this study was to evaluate the efficacy and tolerability of robenacoxib for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs. The study was a prospective, randomized, blinded, positive-controlled, non-inferiority, multi-center clinical trial. A total of 174 dogs undergoing major soft tissue surgery were included and randomly allocated in a 2:1 ratio to receive either robenacoxib (n = 118) or the positive control, meloxicam (n = 56). Each dog received an initial dose subcutaneously prior to surgery (robenacoxib 2 mg/kg, meloxicam 0.2 mg/kg), followed by daily oral doses (robenacoxib 1-2 mg/kg, meloxicam 0.1 mg/kg) for 12 days (range 10-14) after surgery. Pain and inflammation were assessed subjectively using the Glasgow Composite Pain Scale (GCPS) by clinicians as the primary end point and additional evaluations by the clinicians and animal owners as secondary endpoints.. Both treatments provided similar pain control, with no significant differences between groups for any efficacy variable using non-parametric analyses (Mann-Whitney U test). In no dog was analgesic rescue therapy administered. Non-inferior efficacy of robenacoxib compared to meloxicam was demonstrated statistically for the primary and all secondary endpoints using parametric analysis of variance, although the data were not normally distributed even after log transformation. For the primary endpoint (reciprocal of the modified GCPS score), the relative efficacy of robenacoxib/meloxicam was 1.12 with a 95% confidence interval of 0.97-1.29.. A treatment regimen of robenacoxib by subcutaneous injection followed by oral tablets had good tolerability and non-inferior efficacy compared to meloxicam for the management of peri-operative pain and inflammation associated with soft tissue surgery in dogs.

Topics: Animals; Cyclooxygenase 2 Inhibitors; Diphenylamine; Dogs; Double-Blind Method; Female; Hydrocortisone; Inflammation; Male; Meloxicam; Pain; Pain Measurement; Phenylacetates; Prospective Studies; Statistics, Nonparametric; Thiazines; Thiazoles

Two experiments evaluated the effects of band castration and oral administration of an analgesic in association with castration on performance and behavioral and physiological responses in yearling beef bulls. In Exp. 1 Angus and Charolais-crossbred bull calves (n = 127; 309.8 ± 59.04 kg BW) and in Exp. 2 Hereford, Angus, and Hereford × Angus crossbred bulls (n = 30; 300.8 ± 4.96 kg BW) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) band castration (BAND), 2) band castration with oral administration of meloxicam (BAND-MEL), and 3) sham castration (SHAM). The BAND and SHAM procedures were completed on d 0. The SHAM treatment consisted of all animal manipulations associated with band castration without band application. Meloxicam was administered on d -1, 0, and 1 (1.0, 0.5, and 0.5 mg/kg, respectively) via an oral bolus. Body weight and a subjective chute score (CS) were collected on d -1, 0, 1, 7, 14, and 21 (d 28 Exp. 1 only). In Exp. 2, jugular blood samples were collected immediately before castration and 24 h postcastration for substance P (SP) analysis. In Exp. 2, video documentation on d 0 was used to determine range of vertical head motion (DIST) on a subset of animals during treatment administration. In both experiments, ADG was similar (P ≥ 0.50) between BAND and BAND-MEL, but ADG in SHAM cattle was greater (P < 0.001) and tended (P = 0.07) to be greater than castrates in Exp. 1 and 2, respectively. In Exp. 1, CS did not differ (P ≥ 0.26) between BAND and BAND-MEL on any day, but castrates exhibited less desirable CS on d 1 and 28 than SHAM cattle. In Exp. 2, CS was not affected (P ≥ 0.41) by castration or the presence of meloxicam. In Exp. 2, DIST did not differ (P = 0.57) between BAND and BAND-MEL, but when pooled, castrates exhibited greater (P = 0.04) DIST than SHAM. In Exp. 2, plasma SP concentrations were similar between BAND and BAND-MEL (P = 0.81) and between castrates vs. sham cattle (P = 0.67). Results indicate no impact of meloxicam administration on performance or behavioral and physiological responses to band castration. However, there was a negative impact of castration on ADG and DIST.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cattle; Cattle Diseases; Housing, Animal; Male; Meloxicam; Orchiectomy; Pain; Thiazines; Thiazoles; Time Factors; Weaning

Farrowing is an intrinsically risky process for both the sow and the piglets that can cause welfare and economic problems. The effects of the non-steroidal anti-inflammatory drug meloxicam on post-farrowing behaviour of sows, and the performance of piglets were investigated. A total of 48 sows were randomly allocated at the day of farrowing (day 0) into two homogeneous groups regarding parity, and treated with either meloxicam or saline solution as placebo. For each sow, number of position changes, total time lying and standing or sitting, feed intake and rectal temperature (RT) were recorded during 3 days after farrowing. Piglets were individually weighed at farrowing and at weaning. The number of position changes did not show significant differences between treatments (P = 0.79). Sows spent significantly less time lying during day +3 after farrowing in the meloxicam group than in the placebo group (P = 0.04). Feed intake and RT showed a parity effect (P < 0.001 in both cases); however, no treatment effect was observed (P = 0.67 and P = 0.47, respectively). Pre-weaning mortality rate in piglets was not affected by treatment. In litters from multiparous sows, piglets of low birth weight (defined as percentile 15: BW <1180 g) had an average daily gain significantly higher in the meloxicam group than in the placebo group (196.6 ± 7.2 v. 166.6 ± 9.1 g/day; P = 0.03). Although the administration of meloxicam 90 min after farrowing showed a positive effect on the total time lying of the sows, additional investigations are required to better qualify relevant indicators of pain following farrowing in sows and to specify the analgesic effects of meloxicam on piglet performance.

Topics: Animal Husbandry; Animal Welfare; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Inflammation; Meloxicam; Motor Activity; Pain; Parity; Parturition; Swine; Swine Diseases; Thiazines; Thiazoles

The aim of this study was to prospectively evaluate the efficacy and tolerability of hyaluronic acid (HA) and meloxicam for the treatment of knee pain due to Kashin-Beck disease (KBD). A total of 162 patients with KBD-based knee pain were randomly assigned to treatment with a 3-week course of HA (n = 80) and a 12-week course of meloxicam (n = 82). Clinical assessments for each patient were made at 0 (baseline), 1, 2, 4, 8, and 12 weeks. The primary efficacy measure was visual analog scale (VAS) pain score. Second efficacy measures comprised the Western Ontario and McMaster Universities (WOMAC) A (pain), B (stiffness), and C (function) scores as well as patients' and physicians' global assessments. Tolerability was evaluated based on adverse events (AEs) and physician reporting. The VAS rapidly decreased in both groups over 12 weeks. The VAS improvement observed in HA group was lower at week 1 (p = 0.001) but better at weeks 8 and 12 (p < 0.001) than the meloxicam group, which were supported by the secondary variables of WOMAC A (p = 0.001) and WOMAC C (p < 0.001) scores and the global assessments of the patients and their physicians (p = 0.020 and 0.003, respectively). No serious AEs were reported, and the overall incidence of AEs among patients treated with meloxicam was higher than in patients treated with HA (p = 0.012). This study suggests that intra-articular injection of HA and administration of oral meloxicam should be efficacious and well tolerated in the treatment of knee pain due to KBD; the onset of action of meloxicam was faster than that of HA, whereas HA therapy resulted in a more prolonged increasing improvement of symptoms than meloxicam. In addition, HA treatment was likely superior to meloxicam with respect to tolerability. Other randomized double-blind studies are needed to confirm the findings of our open-label study.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Hyaluronic Acid; Injections, Intra-Articular; Kashin-Beck Disease; Knee Joint; Male; Meloxicam; Middle Aged; Pain; Pain Measurement; Single-Blind Method; Thiazines; Thiazoles; Treatment Outcome; Viscosupplements

To evaluate the analgesic efficacy of the NSAIDs flunixin and meloxicam administered locally to the scrotum before ring castration.. Randomised, controlled, prospective study.. Forty eight single born male Merino lambs.. Lambs, aged approximately 4 weeks, were allocated to four groups for castration. Groups were: sham control; castration + saline; castration + flunixin; castration + meloxicam. Drugs (5 mL) were administered subcutaneously around the circumference of the scrotum immediately before castration. Cortisol, rectal temperature, haematology and plasma haptoglobin were measured before and up to 48 hours after treatment. Behaviour recorded by video for 12 hours after treatment was classified as pain avoidance behaviours in the first hour and postural behaviours in three 4 hour intervals.. Ring castration (saline group) induced a bi-phasic increase in cortisol with peaks at 90 minutes and 24 hours but no significant changes in haematology, haptoglobin or rectal temperature. Pain avoidance behaviours were increased and teat seeking decreased. Normal lying and normal standing postures were decreased and abnormal ventral lying, statue standing, abnormal standing and total abnormal postures increased. Flunixin decreased cortisol at 90 minutes (60.3 versus 117.3 nmol L(-1) ) and cortisol AUC (0-6 hours), decreased elevated leg movement (2.5 versus 5.4 events) and sum of pain avoidance behaviours (8.5 versus 16.7 events), improved time spent in normal ventral lying and decreased abnormal ventral lying and total abnormal postures compared to saline treated lambs. In a similar contrast, meloxicam caused non-significant decreases in cortisol at 90 minutes, cortisol AUC (0-6 hours) and pain avoidance behaviours, and significantly improved the postural behaviours normal ventral lying (26.7 versus 15.4%) and normal standing (13.9 versus 7.5%), and reduced abnormal standing and total abnormal postures. Physiological and behavioural responses associated with ring castration for both NSAID treatment groups were generally greater than sham controls.. Locally administered NSAIDs provided partial analgesia for ring castration.

Topics: Analgesics; Animals; Behavior, Animal; Body Temperature; Clonixin; Drug Administration Schedule; Hydrocortisone; Male; Meloxicam; Orchiectomy; Pain; Sheep; Sheep Diseases; Thiazines; Thiazoles; Weight Gain

Dehorning is common in the cattle industry, and there is a need for research evaluating pain mitigation techniques. The objective of this study was to determine the effects of oral meloxicam, a non-steroidal anti-inflammatory, on cattle behavior post-dehorning by monitoring the percent of time spent standing, walking, and lying in specific locations within the pen using accelerometers and a remote triangulation device. Twelve calves approximately ten weeks of age were randomized into 2 treatment groups (meloxicam or control) in a complete block design by body weight. Six calves were orally administered 0.5 mg/kg meloxicam at the time of dehorning and six calves served as negative controls. All calves were dehorned using thermocautery and behavior of each calf was continuously monitored for 7 days after dehorning using accelerometers and a remote triangulation device. Accelerometers monitored lying behavior and the remote triangulation device was used to monitor each calf's movement within the pen.. Analysis of behavioral data revealed significant interactions between treatment (meloxicam vs. control) and the number of days post dehorning. Calves that received meloxicam spent more time at the grain bunk on trial days 2 and 6 post-dehorning; spent more time lying down on days 1, 2, 3, and 4; and less time at the hay feeder on days 0 and 1 compared to the control group. Meloxicam calves tended to walk more at the beginning and end of the trial compared to the control group. By day 5, the meloxicam and control group exhibited similar behaviors.. The noted behavioral changes provide evidence of differences associated with meloxicam administration. More studies need to be performed to evaluate the relationship of behavior monitoring and post-operative pain. To our knowledge this is the first published report demonstrating behavioral changes following dehorning using a remote triangulation device in conjunction with accelerometers.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cattle; Horns; Male; Meloxicam; Pain; Remote Sensing Technology; Thiazines; Thiazoles

Dehorning is a common practice involving calves on dairy operations in the United States. However, less than 20% of producers report using analgesics or anesthetics during dehorning. Administration of a systemic analgesic drug at the time of dehorning may be attractive to dairy producers since cornual nerve blocks require 10 - 15 min to take effect and only provide pain relief for a few hours. The primary objectives of this trial were to (1) describe the compartmental pharmacokinetics of meloxicam in calves after IV administration at 0.5 mg/kg and (2) to determine the effect of meloxicam (n = 6) or placebo (n = 6) treatment on serum cortisol response, plasma substance P (SP) concentrations, heart rate (HR), activity and weight gain in calves after scoop dehorning and thermocautery without local anesthesia.. Plasma meloxicam concentrations were detectable for 50 h post-administration and fit a 2-compartment model with a rapid distribution phase (mean T(1/2α) = 0.22 ± 0.087 h) and a slower elimination phase (mean T(1/2β) = 21.86 ± 3.03 h). Dehorning caused a significant increase in serum cortisol concentrations and HR (P < 0.05). HR was significantly lower in the meloxicam-treated calves compared with placebo-treated calves at 8 h (P = 0.039) and 10 h (P = 0.044) after dehorning. Mean plasma SP concentrations were lower in meloxicam treated calves (71.36 ± 20.84 pg/mL) compared with control calves (114.70 ± 20.84 pg/mL) (P = 0.038). Furthermore, the change in plasma SP from baseline was inversely proportional to corresponding plasma meloxicam concentrations (P = 0.008). The effect of dehorning on lying behavior was less significant in meloxicam-treated calves (p = 0.40) compared to the placebo-treated calves (P < 0.01). Calves receiving meloxicam prior to dehorning gained on average 1.05 ± 0.13 kg bodyweight/day over 10 days post-dehorning compared with 0.40 ± 0.25 kg bodyweight/day in the placebo-treated calves (p = 0.042).. To our knowledge, this is the first published report examining the effects of meloxicam without local anesthesia on SP, activity and performance of calves post-dehorning. These findings suggest that administration of meloxicam alone immediately prior to dehorning does not mitigate signs of acute distress but may have long term physiological, behavior and performance effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cattle Diseases; Heart Rate; Horns; Hydrocortisone; Meloxicam; Pain; Substance P; Thiazines; Thiazoles; Weight Gain

Vasectomized mice are needed in the production of genetically-modified animals. The BVAAWF/FRAME/RSPCA/UFAW Joint Working Group on Refinement recommended that vasectomy should be performed via an incision in the scrotal sac, rather than via laparotomy, arguing that the former could be less painful due to minimal tissue trauma. This study was undertaken to assess the validity of this recommendation. Mice underwent vasectomy via either abdominal or scrotal approach surgery. Mice were filmed for 15 min presurgery and at one, 24 and 48 h postsurgery. Data were obtained using automated behaviour recognition software (HomeCageScan). Meloxicam was administered either alone or combined with acetaminophen prior to surgery. A third group received only saline subcutaneously. Postsurgery behaviour changes were compared between groups at each time point. Exploratory behaviours such as rearing, walking and sniffing were most greatly reduced at one hour following surgery whereas the duration of grooming increased. By 48 h these changes had largely subsided. Results indicated mice undergoing scrotal approach surgery fared better at one hour postsurgery, but the magnitude of this was relatively insignificant compared with the overall effects of surgery. If the observed behaviour changes resulted from pain, results suggested there was no significant advantage of scrotal versus abdominal approach vasectomy. These and other recently obtained data on the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in mice suggest considerably larger doses of these or more potent analgesics, more precise monitoring of surgical outcomes, or a combination of these factors are needed to determine the extent of pain experienced by mice undergoing vasectomy.

Topics: Abdomen; Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Drug Combinations; Image Processing, Computer-Assisted; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Meloxicam; Mice; Pain; Pain Measurement; Pilot Projects; Scrotum; Surgery, Veterinary; Thiazines; Thiazoles; Time Factors; Vasectomy; Videotape Recording

The objective of this study was to compare the efficacy and tolerability of celecoxib, meloxicam and paracetamol in late Kashin-Beck disease. Adults (n = 168) with Kashin-Beck disease were randomised in clusters to receive six week courses of celecoxib 200 mg once daily, meloxicam 7.5 mg once daily or paracetamol 300 mg three times daily. Efficacy assessments included overall joint pain intensity and Western Ontario and McMaster Universities Osteoarthritis Index subscales; tolerability was evaluated by adverse event and physician reporting. Celecoxib and meloxicam were efficacious in relieving pain and improving stiffness, but unable to improve physical function after six weeks. Paracetamol was efficacious in relieving pain, but unable to improve morning stiffness and physical function after six weeks. Celecoxib and meloxicam provide predictable and sustained relief from pain and stiffness. Paracetamol can relieve the pain. None of the treatments improved impaired physical function in Kashin-Beck disease.

Topics: Acetaminophen; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Female; Health Status; Humans; Joints; Kashin-Beck Disease; Male; Meloxicam; Middle Aged; Pain; Pain Measurement; Pyrazoles; Sulfonamides; Thiazines; Thiazoles; Treatment Outcome; Young Adult

The pharmacokinetics and analgesic effect of the nonsteroidal anti-inflammatory drug meloxicam (0.5 mg/kg) in goats were investigated. In a randomized, cross-over design the pharmacokinetic parameters were investigated in adult goats (n = 8) after single intravenous and oral administration. The analgesic effect was evaluated in kids using a randomized, placebo controlled and blinded protocol. Kids received meloxicam (n = 6) once daily and their siblings (n = 5) got isotonic NaCl intramuscularly while still anaesthetized after cautery disbudding and injections were repeated on three consecutive days. In the adult goats after intravenous administration the terminal half-life was 10.9 ± 1.7 h, steady-state volume of distribution was 0.245 ± 0.06 L/kg, and total body clearance was 17.9 ± 4.3 mL/h/kg. After oral administration bioavailability was 79 ± 19%, C(max) was 736 ± 184 ng/mL, T(max) was 15 ±5 h, although the terminal half-life was similar to the intravenous value, 11.8 ± 1.7 h. Signs of pain using a visual analogue scale were smaller in kids treated with meloxicam compared with kids treated with placebo on the first day after disbudding, but subsequently no difference in pain was noticeable. Plasma cortisol and glucose concentrations did not differ between the two groups.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Blood Glucose; Goat Diseases; Goats; Half-Life; Hydrocortisone; Meloxicam; Pain; Surgical Procedures, Operative; Thiazines; Thiazoles

The aim of this study was to evaluate the efficacy and palatability of meloxicam 0.5mg/ml oral suspension, compared to ketoprofen tablets in cats suffering from painful acute locomotor disorders. This single blinded, positively-controlled, randomised, multicentre trial involved 121 client owned cats. Cats received either meloxicam (0.5mg/ml oral suspension) at 0.1mg/kg on day 1 followed by 0.05mg/kg q 24h on days 2-5, or ketoprofen 5mg tablets at 1.0mg/kg q 24h for 5 days. The efficacy of the two treatments was assessed subjectively by clinicians on day 6 using a clinical sum score (CSS). Palatability and accuracy of dosing were also assessed. The baseline CSS was not significantly different between the groups, and after 5 days of treatment the CSS had decreased to a similar extent, reflecting a reduction in pain. There were no significant differences between the CSS of each group at day 6. Both treatments were well tolerated. Meloxicam was significantly more palatable than ketoprofen, and allowed for more accurate dosing. Meloxicam and ketoprofen are a safe and efficacious treatment for acute locomotor disorders in cats. Meloxicam (Metacam) may be associated with superior compliance in clinical practice due to the higher palatability, which results in better ease of administration.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Female; Ketoprofen; Lameness, Animal; Male; Meloxicam; Pain; Pain Measurement; Taste; Thiazines; Thiazoles; Treatment Outcome

To determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis.. Randomized, blinded, controlled, and four-way crossover study.. Eight surgically neutered cats (four males, four females) paired according to sex.. Each pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg(-1) oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL(-1) SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response-time curve (AUC(0-30) hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result.. Meloxicam at doses of 0.05 and 0.075 mg kg(-1) day(-1) PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC(0-30) hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC(0-30) hours of AS, LS, and VAS).. The lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg(-1) day(-1) PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cats; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Male; Meloxicam; Pain; Pain Measurement; Single-Blind Method; Synovitis; Thiazines; Thiazoles; Treatment Outcome; Uric Acid

A double-blind trial was performed on 12 client-owned dogs suffering from acute and painful dermatitis. Clinically these cases represented pyotraumatic dermatitis and pyotraumatic folliculitis. Six dogs were injected with meloxicam and 6 were given placebo. Signs of pain were recorded on a visual analogue scale before administering the drug. This was repeated over the following 2-3 days. All dogs were treated with cephalexin orally. Six dogs given meloxicam and cephalexin showed an average decrease of pain on day 2 of 28.3%, whereas the 6 dogs given placebo and cephalexin showed an average decrease of pain on day 2 of 8.3%. When compared in the Wilcoxon two-sample test, using change in percent and absolute change, the 2 groups yielded p = 0.026 and p = 0.064 respectively. These findings indicate that meloxicam has an analgesic effect on acute dermatitis in dogs.

Topics: Acute Disease; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cephalexin; Dermatitis; Dog Diseases; Dogs; Double-Blind Method; Meloxicam; Pain; Pain Measurement; Pilot Projects; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

In this randomised, multicentre clinical study, dogs with musculoskeletal pain and inflammation were treated with either vedaprofen or meloxicam administered orally at the recommended dose rates. Clinical examinations were carried out regularly and clinical severity scores assigned. In total, 214 cases (73 acute, 141 chronic) were evaluated. Treatment with vedaprofen and meloxicam was continued for 14 and 17 days, respectively, in the acute cases, and 38 and 39 days in the chronic cases. NSAID treatment resulted in a significant improvement in clinical scores. The overall response to treatment ('responders') at the final clinical examination was 89 per cent and 87 per cent in the acute cases and 72 per cent and 65 per cent in the chronic cases in the vedaprofen and meloxicam groups, respectively. Mild transient gastrointestinal signs were observed in both groups (11 per cent vedaprofen, 12 per cent meloxicam). Adverse effects related to NSAIDs resulted in treatment cessation in 5 per cent of the dogs in each group. Vedaprofen and meloxicam were efficacious in, and well tolerated by, most of the dogs in the study.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Dog Diseases; Dogs; Female; Inflammation; Male; Meloxicam; Musculoskeletal Diseases; Naphthalenes; Pain; Propionates; Thiazines; Thiazoles; Treatment Outcome

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

Topics: Adult; Aged; Arachidonic Acid; Cyclooxygenase Inhibitors; Digestive System; Dinoprostone; Double-Blind Method; Endoscopy, Digestive System; Female; Gastric Juice; Humans; Leukotriene B4; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Piroxicam; Safety; Thiazines; Thiazoles; Thromboxane B2

The ability of two non-steroidal anti-inflammatory drugs to modify the clinical manifestations of pain associated with locomotor disease was assessed. Sixty-nine cats with acute or chronic locomotor disorders were recruited from 14 first opinion UK veterinary practices and randomly allocated to one of two treatment groups. Group A received meloxicam drops (0.3 mg/kg orally on day 1 followed by 0.1 mg/kg daily for four more consecutive days) and group B received ketoprofen tablets (1.0 mg/kg orally once daily for five days). Each cat underwent a full clinical examination before treatment, 24 hours after initiation of treatment and 24 hours after completion of treatment. General clinical parameters (demeanour and feed intake) and specific locomotor parameters (weightbearing, lameness, local inflammation and pain on palpation) were scored using a discontinuous scale scoring system. The two groups did not differ in terms of age, weight, gender distribution or duration of clinical signs; nor did they differ in terms of general clinical or specific locomotor scores pretreatment. Both treatment regimens resulted in a significant improvement in demeanour, feed intake and weightbearing, and a significant reduction in lameness, pain on palpation and inflammation. No significant difference was observed between the two treatment groups with respect to any of the parameters measured and both treatments were associated with minimal observed side effects. Meloxicam and ketoprofen were found to be effective analgesics and well tolerated in cats with acute or chronic locomotor disorders when administered for short-term treatment (five days) in such cases. However, meloxicam was assessed to be significantly more palatable than ketoprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Female; Ketoprofen; Lameness, Animal; Male; Meloxicam; Pain; Pain Measurement; Thiazines; Thiazoles; Treatment Outcome

To evaluate the efficacy and safety of meloxicam, a new acidic enolic nonsteroidal anti-inflammatory drug, at doses of 7.5 and 15 mg once daily in patients with rheumatoid arthritis (RA).. Meloxicam 15 and 7.5 mg daily was administered for 21 days in this double blind, randomized, placebo controlled study. 159 patients received meloxicam 7.5 mg, 162 received meloxicam 15 mg, and 147 received placebo.. Meloxicam 15 mg once daily was significantly superior (p < 0.05) to placebo in 3 of the 4 primary endpoints (disease activity assessed by the investigator, disease activity assessed by the patient, and reduction of the number of tender/painful joints). No difference was observed regarding number of swollen joints. The difference between meloxicam 7.5 mg once daily and placebo reached statistical significance in 2 of the 4 primary endpoints, disease activity assessed by the patient and number of tender/painful joints. A statistically significant difference between meloxicam 1.5 mg and 7.5 mg was not observed for any primary endpoint. The rating of global tolerance by investigators and patients at the end of the study was similar in the 3 treatment groups, indicating that meloxicam and placebo were generally similarly well tolerated. However, there was a slightly higher incidence of gastrointestinal (GI) disturbances reported by patients receiving meloxicam 15 mg. GI adverse events were reported by 11, 11, and 16% of patients in the placebo, meloxicam 7.5 mg, and meloxicam 15 mg groups, respectively. None were serious.. Meloxicam in daily doses of 7.5 and 15 mg is effective in treating the signs and symptoms of RA.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Demography; Double-Blind Method; Female; Humans; Joints; Male; Meloxicam; Middle Aged; Pain; Safety; Thiazines; Thiazoles; Treatment Outcome

In this controlled, randomised, parallel-group, multicentre study, the efficacy and tolerability of an intramuscular (i.m.) dose of meloxicam (15 mg) on Day 1 followed by seven days of oral meloxicam (15 mg/day) were compared with those of an i.m. dose of piroxicam (20 mg) on Day 1 followed by seven days of oral piroxicam (20 mg/day) therapy in a total of 169 outpatients with acute lumbago. Time to onset of analgesic action after i.m. injection was determined, and overall efficacy, pain on movement, limitation of daily activities, local tolerability at the injection site and overall tolerability were assessed by investigators and patients on verbal rating scales (VRSs). Adverse events and laboratory assessments were documented. Meloxicam and piroxicam showed a rapid onset of action after i.m. injection (40 and 45 minutes median time, respectively), overall efficacy of both therapies was highly rated, and limitations to daily life were greatly reduced in the majority of patients in both groups. There were no statistically significant differences in efficacy between meloxicam and piroxicam. Local and overall tolerabilities were equally good for the two drugs, but there were fewer gastrointestinal (GI) adverse events among meloxicam patients (1.2% of patients) than piroxicam patients (7.0% of patients). The improved tolerability profile of meloxicam may be explained by its selectivity towards cyclooxygenase-2.

Topics: Activities of Daily Living; Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Chi-Square Distribution; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Low Back Pain; Male; Meloxicam; Middle Aged; Movement; Pain; Pain Measurement; Piroxicam; Thiazines; Thiazoles

Acute kidney injury (AKI) is a well-known but poorly documented adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) in cats. We aimed to describe instances of NSAID-associated AKI in cats and survey Australian veterinarians on NSAID use in acute settings.. Medical records of cats that developed an AKI subsequent to the administration of meloxicam were obtained by searching the databases of seven practices in Queensland, as well as by contemporaneously contacting select veterinary colleagues of the authors in both general and specialist small animal practice. An online questionnaire was created for the survey, and the URL distributed to Australian practitioners.. A total of 18 cases were retrieved, all of which received injectable meloxicam. The indication(s) for its use and the dosage prescribed were within the manufacturer's recommendations for Australian veterinarians. The majority of cases (13/18 cats) received the label dose of 0.3 mg/kg subcutaneously (SC) on the day of the procedure. In 12/18 cats, the injection was given in association with general anaesthesia or sedation. Fourteen cats survived to hospital discharge. Of 187 survey respondees, 89% routinely administered NSAIDs for surgery-related analgesia, with 98% prescribing meloxicam and 84% of these giving it SC. Ninety percent of respondees routinely administered NSAIDs for non-surgical-related analgesia, with 99% prescribing meloxicam and 35% of those giving it SC.. We strongly recommend that practitioners avoid prescribing meloxicam SC in cats. This recommendation is emphatic in situations where concurrent dehydration and/or hypotension are possible.

Topics: Acute Kidney Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Australia; Cat Diseases; Cats; Meloxicam; Pain; Thiazines

Flunixin meglumine (FM), a nonselective cyclooxygenase (COX) inhibitor, is most frequently selected for the treatment of equine systemic inflammatory response syndrome (SIRS)/endotoxemia. However, FM has considerable adverse effects on gastrointestinal function. The aims of this study were to compare the effect of meloxicam (MX), a COX-2 selective inhibitor commonly used in equine clinical practice, with FM, and to investigate the potential for clinical application in horses with SIRS/endotoxemia. Fifteen horses were divided into three groups of five and orally administered MX (0.6 mg/kg), FM (1.1 mg/kg), or saline as placebo at 30 minutes after LPS challenge. Clinical parameters, including behavioral pain scores, were recorded and blood for clinical pathological data was collected at various times from 60 minutes before to 420 minutes after LPS infusion. The pain score were significantly lower in both the MX and FM groups than in the placebo group, with no significant difference between them. Body temperature was significantly lower in the MX and FM groups than in the placebo group. Heart rates and respiratory rates, hoof wall surface temperature, and leukocyte counts changed similarly between the MX and FM groups. TNF-α and cortisol were lower in the FM group than in the MX group. The results suggest that MX suppresses the inflammatory response after LPS infusion and has an analgesic effect similar to that of FM. Given the adverse effects of nonselective COX inhibitors, clinical application of MX may be beneficial in horses with SIRS/endotoxemia.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Endotoxemia; Horse Diseases; Horses; Lipopolysaccharides; Meloxicam; Pain

Meloxicam is a nonsteroidal anti-inflammatory analgesic drug that is often used in mice. However, doses of 1 to 5 mg/kg given twice daily were recently reported to provide inadequate analgesia. Some studies suggest that doses of up to 20 mg/kg may be necessary for adequate pain management. We investigated the analgesia provided by a high-dose of meloxicam in female CD1 mice. Pharmacokinetic analyses demonstrated that a subcutaneous injection of 10 mg/kg or 20 mg/kg of meloxicam produced therapeutic plasma concentrations for at least 12 h. Ovariectomies via ventral laparotomy were performed to assess analgesic efficacy. Mice were treated immediately before surgery with a high-dose of 10 mg/kg, a low-dose of 2.5 mg/kg, or saline, followed by every 12 h for 36 h. At 3, 6, 12, 24, and 48 h after surgery, mice were assessed for pain based on the following behaviors: distance traveled, time mobile, grooming, rearing, hunched posture, orbital tightening, and von Frey. Initially, some mice received a 20-mg/kg loading dose followed by 10 mg/kg every 12 h. This regimen caused severe morbidity and mortality in 2 mice. Subsequently, this regimen was abandoned, and mice assigned to the high-dose group received 10 mg/kg every 12 h. Mice that received the 10-mg/kg dose after surgery showed less orbital tightening between 3 to 6 h and reduced frequency of hunched posture for 48 h compared with mice that received either the low-dose or saline. However, mice were significantly less mobile for 6 to 12 h after surgery regardless of treatment. These data indicate that a meloxicam dose of 10 mg/kg every 12 h provides better analgesia than a 2.5-mg/kg dose but does not completely alleviate pain.

Topics: Analgesia; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Meloxicam; Mice; Pain; Pain Management; Pain, Postoperative; Thiazines

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Cyclooxygenase 2; Dinoprostone; Dog Diseases; Dogs; Meloxicam; Pain; Protein Isoforms; Rabbits; Thiazines; Thiazoles

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Osteoarthritis; Pain; Rats; Rats, Wistar; Thiazines

Hot-iron disbudding, the practice of cauterizing horn bud tissue to prevent horn growth in dairy calves, results in behavioral changes indicative of pain in the first few days after the procedure. However, few studies have quantified behavioral changes in the following weeks, while the burn wounds are still healing. Female Holstein calves were disbudded with a heated iron and pain relief (5.5 mL lidocaine cornual nerve block and 1 mg/kg oral meloxicam) at 4 to 10 d of age (n = 19) or not disbudded (n = 19). Calves wore ear tag accelerometers that reported the dominant behavior being performed at 1-min intervals from 3 to 21 d after disbudding. Compared with age-matched controls, disbudded calves tended to spend more time inactive throughout the observation period, ruminated less in the first 3 to 11 d after disbudding, and sucked more from a milk bottle beginning 5 d after disbudding until the end of the 21-d observation period. In addition to the accelerometer data, live observations of sleeping (using a behavioral proxy), lying, and ruminating were collected using instantaneous sampling at 5-min intervals for 24-h periods 3, 10, and 17 d after disbudding. Disbudded calves slept with their head down more on all live observation days and spent more time lying on the 17th d after disbudding, but ruminating did not differ compared with controls, in contrast to the accelerometer results. More time spent inactive, sleeping, and lying, and less time spent ruminating (as indicated by the accelerometer) can be interpreted as attempts to reduce painful stimulation of the disbudding wounds and allocate energy to healing. It is unclear whether the greater amount of sucking in the disbudded calves is nutritive (milk present) or non-nutritive (milk absent), as the algorithm did not distinguish the type of sucking, and further research is needed to explore the factors underlying this effect. We conclude that disbudding alters daily behavior patterns for at least 3 wk, far beyond the duration of recommended pain medication, raising additional welfare concerns about the procedure.

Topics: Animals; Cattle; Female; Horns; Iron; Lidocaine; Meloxicam; Pain

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their applicability in analgesia if their ceiling and adverse effects are reduced. The aim of this study was to evaluate the pharmacological interaction of two NSAIDs, paracetamol and meloxicam, with the antipsychotic drug risperidone in mice, in several experimental tests of nociceptive and inflammatory pain. Antinociception was assessed by dose-response curves to paracetamol and meloxicam before and after the i.p. administration of 0.5 mg/kg of risperidone. Results are presented as means ± SEM and differences were calculated by one-way ANOVA followed by Tukey's post-test. Paracetamol and meloxicam produced a dose-related antinociceptive effect with diverse potencies. Risperidone increased the analgesia mediated by paracetamol and meloxicam only in the tonic tests that detected inflammatory pain. This suggests that COX inhibition is only a partial explanation of the increased analgesic potency of paracetamol and meloxicam since the effects of NSAIDs in the CNS are mediated by multiple mechanisms. These results indicate that the combination of risperidone with paracetamol or meloxicam could be a new and effective alternative for the management of inflammatory pain.

Topics: Acetaminophen; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Mice; Pain; Risperidone

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of the microneedle patch. Results regarding the physical characteristics, chemical composition, and mechanical properties confirmed that rheological properties of the chitosan solution, present significant differences over time, demonstrating that reusing the solution on the fourth day results in failure patches. Morphological characteristics and chemical composition studies revealed that the process of sterilization (ethylene oxide gas) needed for implanting the patches into the skin did not affect the properties of microneedle patches. In-vitro studies showed that approximately 33.02 ± 3.88% of the meloxicam was released over 7 days. A full penetration of the microneedles into the skin can be obtained by applying approximately 3.2 N. In-vivo studies demonstrated that microneedle patches were capable of swelling and dissolving, exhibiting a dissolution percentage of more than 50% of the original height of microneedle after 7 days. No abnormal tissue, swelling, or inflammation was observed in the implanted area. The results of this work show that chitosan biodegradable microneedle patches may be useful to deliver meloxicam to improve pain management of cattle with positive effects for commercial manufacturing.

Topics: Administration, Cutaneous; Animals; Cattle; Chitosan; Drug Delivery Systems; Meloxicam; Needles; Pain; Pain Management; Skin; Transdermal Patch

Meloxicam (MLX) is considered to have significant analgesic properties. However, the analgesic effects of MLX are compromised by its poor water solubility and thus the low drug loading. The purpose of this study was to develop a high drug-loaded MLX injection by formulating it into nanocrystals (NCs) for the treatment of analgesia. The developed MLXNCs exhibited satisfactory particle sizes and remarkably in vitro dissolution behaviors. In addition, the plasma concentrations of MLXNCs were comparable with the MLX solution (formulated with 1.0% polyoxyethylene castor oil 35) in rats. The acetic acid-induced writhing tests, hot plate tests and hind paw incision experiments demonstrated that the MLXNCs had significant analgesic effects. The findings provide insights into the developed high drug-loaded MLXNCs and provide new therapeutic options for acute and chronic pain management.

Topics: Acetates; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Nanoparticles; Pain; Pain Management; Rats; Thiazines; Thiazoles; Water

In Germany, injection and inhalation anesthesia with the addition of an analgesic drug are an interim solution to surgical castration under general anesthesia due to the ban on non-anesthetic castration of male suckling piglets under 8 days of age. However, the efficiency of both anesthetic procedures is submit to controversial discussion. Most of the studies addressing this question only examined one of the procedures in comparison to piglets castrated without anesthesia or uncastrated controls. Comparisons between the anesthesia methods, especially under conditions of organically working farms, are almost completely lacking. The aim of the present study was therefore to compare the efficacy of injection and inhalation anesthesia under practical conditions in 7 organic farms as well as to examine the effect of metamizole administered in addition to meloxicam.. For this purpose, 514 male suckling piglets were examined with regard to anesthesia efficiency (reflex test, defence behaviour), body temperature, post-operative bleeding and wound healing, post-operative behavior and pain behavior as well as the course of the recovery phase.. The results show a basic superiority of inhalation anesthesia over injection anesthesia, especially in the areas of anesthetic efficacy, thermoregulation and duration of the recovery phase. In 7.7 to 15 % of piglets, the perianal and interclaw reflexes studied were still present at the time of castration. Following injection and inhalation anesthesia, in total 83.6 (25.2 %) of the piglets showed at least one of the following criteria: positive reflex response, clear defensive movements or vocalisations. Body temperature dropped by 0.41 °C under inhalation anesthesia and by 1.82 °C under injection anesthesia. Post-castration bleeding and wound healing were hardly influenced by the type of anesthesia. Almost all piglets showed signs of pain and pain-associated behavior for 5 and 72 hours after castration, regardless of the type of anesthesia. The post-castration recovery phases lasted significantly longer after injection anesthesia (107 minutes) than following inhalation anesthesia (33.3 minutes) until the piglets were returned to the sow.. Neither injection nor inhalation anesthesia in spite of additional administration of meloxicam, nor the supplementary use of metamizole, fulfil the EU requirements for painless castration.. The necessary analgesia during and after castration of male suckling piglets is not achieved under either isoflurane or ketamine/azaperone anesthesia, despite the use of meloxicam and metamizole.. Die Effizienz der Injektions- und Inhalationsnarkose zur betäubungslosen Kastration von unter 8 Tage alten männlichen Saugferkeln wird kontrovers diskutiert. Allerdings fehlen direkte Vergleiche zwischen den Narkoseverfahren, insbesondere unter Bedingungen ökologisch arbeitender Betriebe, bislang fast vollständig. Ziel der vorliegenden Untersuchung war es daher, die Effizienz der Injektions- und Inhalationsnarkose auf 7 ökologisch arbeitenden Betrieben unter Praxisbedingungen zu vergleichen und den Effekt von Metamizol zusätzlich zu Meloxicam zu überprüfen.. Hierzu wurden 514 männliche Saugferkel bezüglich Narkoseeffizienz (Perianal- und Zwischenklauenreflex, Abwehrverhalten), Körpertemperatur, Nachblutung und Wundheilung, postoperativem Verhalten und Schmerzverhalten sowie dem Ablauf der Nachschlafphase untersucht.. Die Inhalationsnarkose war der Injektionsnarkose grundsätzlich überlegen, insbesondere bezüglich Narkoseeffizienz, Thermoregulation und Nachschlafphase. Doch waren bei 7,7 bis 15 % der Ferkel die Reflexe zum Zeitpunkt der Kastration noch vorhanden. Nach Injektions- oder Inhalationsnarkose zeigten insgesamt 83,6 bzw. 25,2 % der Ferkel mindestens eines der folgenden Kriterien: positive Reflexantwort, deutliche Abwehrbewegungen, eine deutliche Abwehrintensität oder Lautäußerungen. Die Körpertemperatur fiel unter Inhalationsnarkose um durchschnittlich 0,41 °C, unter Injektionsnarkose um 1,82 °C ab. Fast alle Ferkel zeigten, unabhängig von der Narkoseart, 5 und 72 Stunden nach der Kastration Anzeichen von Schmerz- und schmerzassoziiertem Verhalten. Die Nachschlafphasen dauerten nach Injektionsnarkose mit 107 Minuten bis zum Zurücksetzen der Ferkel an die Sau signifikant länger als nach Inhalationsnarkose (33,3 Minuten).. Weder die Injektions- noch die Inhalationsnarkose unter Einsatz von Meloxicam und auch nicht bei zusätzlicher Anwendung von Metamizol erfüllen die Anforderungen der EU an eine schmerzfreie Kastration.. Die notwendige Schmerzausschaltung während und nach der Kastration männlicher Saugferkel wird weder unter Isofluran noch unter Ketamin/Azaperon-Narkose erreicht, trotz Einsatz von Meloxicam und Metamizol.

Topics: Anesthesia; Animals; Dipyrone; Female; Male; Meloxicam; Orchiectomy; Organic Agriculture; Pain; Swine

To investigate the effect of visual acupotomy intervention on intervertebral disc degeneration, nucleus pulposus cell apoptosis and expression of apoptosis related proteins in rabbits with cervical spondylosis (CS), so as to explore its mechanism underlying improvement of CS.. A total of 48 male New Zealand rabbits were randomly divided into blank control, model, acupotomy and medication (meloxicam) groups, with 12 rabbits in each group. The neck type CS model was established by forcing the rabbit to make a neck flexion for 5 hours in a restrained chamber, once daily for 12 weeks. Rabbits of the medication group received an intramuscular injection of meloxicam (0.35 mg/kg), once daily for 4 consecutive weeks, and those of the acupotomy group received ultrasound-guided acupotomy intervention, once a week for 4 weeks. The pain threshold (PT) was measured by using a VonFrey electronic pain detector. The levels of prostaglandin E2 (PGE2), 5-hydroxytryptamine (5-HT) and substance P (SP) in serum were detected by ELISA. The severity of intervertebral disc degeneration was observed by using magnetic resonance imaging (MRI) and given scores in accordance with Suzuki's and colleague's "new classification system of cervical disk degeneration". The apoptosis of nucleus pulposus cells was analyzed by TUNEL staining. The protein expression levels of apoptosis-related protein Fas, cysteinyl aspartate-specific protease-3 (Caspase-3), B-cell lymphoma-2 asso-ciated X protein (Bax) and B-cell lymphoma-2 protein (Bcl-2) were measured by Western blot.. Compared with the blank control group, the PT and Bcl-2 expression and MRI score were significantly down-regulated (. Visual acupotomy intervention can mitigate the pain state of CS rabbits, which may be related to its functions in improving the intervertebral disc degeneration, reducing inflammatory reactions and apoptosis of nucleus pulposus cells.

Topics: Acupuncture Therapy; Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Dinoprostone; Intervertebral Disc Degeneration; Male; Meloxicam; Nucleus Pulposus; Pain; Proto-Oncogene Proteins c-bcl-2; Rabbits; Serotonin; Spondylosis; Substance P

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.

Topics: Animal Husbandry; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Castration; Clonixin; Dinoprostone; Extracellular Fluid; Hydrocortisone; Ketoprofen; Male; Meloxicam; Pain; Pain Management; Swine; Tail

Repeatable measures of pain in ruminants following husbandry procedures are required to validate responses to pain relief. This study tested the hypotheses that facial action units, activity and time spent with dam can be used to assess the efficacy of pain relief in lambs following mulesing. Merino lambs (n = 120) were allocated to one of six treatments implemented at mulesing: (1) lambs that were not mulesed or lambs that were mulesed and administered (2) no pain relief, (3) meloxicam 15 min before mulesing, (4) Tri-Solfen®, (5) a combination of meloxicam 15 min before mulesing and Tri-Solfen after mulesing and (6) meloxicam at mulesing. Facial action units detected a difference in pain between mulesed and non-mulesed lambs at 1 and 5 h post-mulesing (P = 0.005 and <0.001) but not at 26 h post-mulesing. Lambs that were not mulesed were more active and spent more time with their dams than mulesed lambs (P < 0.001). No differences were observed between lambs that were mulesed with or without pain relief. Therefore, facial action units, activity of the lamb and time spent with dam can detect pain in response to mulesing in Merino lambs but cannot detect any changes associated with pain relief.

Topics: Animal Welfare; Animals; Behavior, Animal; Meloxicam; Pain; Sheep; Sheep, Domestic

Topics: COVID-19; Herpes Zoster; Humans; Meloxicam; Pain; Paresthesia; SARS-CoV-2; Suction

Ovariectomy (spaying) using the trans-vaginal dropped ovary technique (DOT) is performed to prevent pregnancy in cull female beef cattle that are not retained for breeding stock in areas practicing extensive grazing management. There are no reports describing analgesia for this surgical procedure. The objective of this study was to measure behavioral and physiological responses to determine whether an analgesic protocol of BXK [butorphanol (0.01 mg/kg), xylazine (0.02 mg/kg), and ketamine (0.04 mg/kg)] injected intramuscularly (i.m.) before spaying could mitigate procedural and immediate postsurgical pain, and whether oral meloxicam (1 mg/kg) administered at the time of spaying could mitigate postsurgical inflammatory pain. Forty-four red Angus and Angus crossbred yearling heifers (322 ± 27.0 kg BW) were randomly allocated to 1 of 3 groups: PALP (control; palpated but not spayed; n = 14), SPAY (spayed with no analgesia; n = 15), and BXKM (spayed with analgesia; n = 15). Behavioral measurements included visual analog scale (VAS) score, flight speed (FS), stride length (SL), and gait score (GS), as well as activity (lying, standing) and feeding behavior. Physiological measurements included salivary cortisol (SC), haptoglobin (Hp), serum amyloid A (SAA), substance P (SP), complete blood count (CBC), and rectal temperature (RT). Saliva and blood samples were collected, and RT, FS, SL, and GS were measured on day -1, day 0 (time of palpation/spaying), and hours 1, 2, 4, and days 1, 2, 4, and 7 after palpation/spaying. The BXKM heifers had lower SC concentrations than SPAY heifers at 1 h (P = 0.01) and 2 h (P = 0.004). Heifers treated with BXKM had Hp concentrations lower than SPAY heifers at 2 d (P = 0.01), 4 d (P < 0.001), and 7 d (P = 0.008), and lower Hp concentrations than PALP heifers at 4 d (P < 0.001). Concentrations of SAA were greater (P = 0.04) in BXKM heifers than in PALP heifers at 1 h and lower in PALP heifers than in BXKM heifers (P = 0.02) and SPAY heifers (P = 0.05) at 1 d. Heifers in the BXKM group had higher RT than PALP and SPAY heifers at 1 h (P < 0.001) and 2 h (P = 0.004). Results suggest that DOT ovariectomy is acutely stressful and painful and administration of BXK before spaying and meloxicam at the time of spaying mitigated the procedural and postsurgical stress, pain, and inflammation.

Topics: Analgesics; Animal Welfare; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Breeding; Cattle; Female; Inflammation; Meloxicam; Ovariectomy; Ovary; Pain

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)-1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug, is under development for the treatment of moderate to severe pain. This single-center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam- or ketorolac-treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin-induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5- and 5-µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.

Topics: Adenosine Diphosphate; Administration, Intravenous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Specimen Collection; Collagen; Cyclooxygenase Inhibitors; Drug Compounding; Epinephrine; Female; Healthy Volunteers; Hemorrhage; Humans; Ketorolac; Male; Meloxicam; Nanoparticles; Pain; Platelet Aggregation; Platelet Function Tests; Reagent Kits, Diagnostic

Animals that experience painful procedures as neonates are more sensitive to pain later in life. We evaluated whether disbudding with a heated iron at 3 (n = 12), 35 (n = 9), or 56 (n = 20) d of age affected heifers' pain responses to vaccine injections at 11 mo of age. Heifers responded to the injection procedure with struggling and changes in eye temperature and heart rate variability compared to a sham procedure the day before, and still had a heightened response 6 d later, regardless of disbudding age. However, some heart rate variability indices suggested increased sympathetic dominance in heifers disbudded at 35 d, compared to the other 2 age groups, independent of the injection procedure. We also found that heifers disbudded at 3 or 35 d had a higher mean heart rate after the injection procedure compared to those disbudded at 56 d. We conclude that: (1) heifers find injections aversive; and (2) there is some evidence that disbudding age influences autonomic nervous system activity later in life.

Topics: Analgesics; Animal Husbandry; Animals; Animals, Newborn; Behavior, Animal; Burns; Cattle; Cohort Studies; Female; Heart Rate; Horns; Injections; Meloxicam; Pain; Vaccination; Vaccines

Evaluate the frequency, nature and course of PTP, as well as the effectiveness and safety of NSAIDs in PTP in real clinical practice.. The assessment of the condition and need for NSAIDs (original meloxicam) in 1115 outpatient patients who suffered a fracture of the radius (32.2%), injury to the knee (35.2%) or ligaments of the ankle (32.6%); women/men 51.5 and 48.5%, average age 46.915.5 years. We evaluated the dynamics of pain intensity (on a numerical rating scale NRS 010) at rest and during movement, the preservation of moderate and severe pain, as well as the development of adverse drugs reactions (ADR) to NSAIDs 48 weeks after injury.. The average intensity of pain during movement decreased from 7.031.66 to 2.211.38 (p0.001), at rest from 4.462.07 to 0.710.989 (p0.001). The number of people with pain severity 4 in the NRS in 48 weeks after the radius fracture, injury of the knee and ligaments of ankle was 21.0, 16.9 and 11.9%, with moderate or severe impairment of the injured limb 40.4, 26.2 and 16.3%, respectively. The need for taking NSAIDs up to 7 days was noted in 43.3%, 714 days-in 41.8%, more than 2 weeks or constantly in 14.9% of patients. Weak or moderate ADR were observed in 20.8% of patients, mainly dyspepsia and hypertension. Discontinuation of NSAIDs due to ADR was required in only 2.6% of patients. Pain retention 4 in NRS was associated with initially expressed pain (7 in NRS) OR 2.75 (95% CI 0.834.13; p0.001) and the presence of osteoarthritis of knee and/or hip OR 1.56 (95% CI 1.032.34; p=0.039).. PTP decreases rapidly in most patients after a radius fracture, injury of the knee, and ankle ligament injury while taking the original meloxicam. However, in a significant part of patients, moderate or severe PTP persists after 48 weeks, which requires prolonged analgesic therapy and active rehabilitation.. Посттравматическая боль (ПТБ) вызывает серьезные страдания и существенно снижает качество жизни пациентов, перенесших острые травмы. Для контроля ПТБ в амбулаторной практике наиболее часто используют нестероидные противовоспалительные препараты (НПВП). Цель. Оценить частоту, характер и течение ПТБ, а также эффективность и безопасность НПВП при ПТБ в реальной клинической практике. Материалы и методы. Проведена оценка состояния и потребности в приеме НПВП (оригинальный мелоксикам) у 1115 амбулаторных пациентов, перенесших перелом лучевой кости ЛК (32,2%), травму области коленного сустава КС (35,2%) или связок области голеностопного сустава ГС (32,6%); женщины/мужчины 51,5 и 48,5%, средний возраст 46,915,5 года. Оценивались динамика интенсивности боли (по числовой рейтинговой шкале ЧРШ 010) в покое и при движении, сохранение умеренной и выраженной боли, а также развитие нежелательных реакций (НР) НПВП через 48 нед после травмы. Результаты. В целом по группе средняя интенсивность боли при движении снизилась с 7,031,66 до 2,211,38 (p0,001), в покое с 4,462,07 до 0,710,989 (p0,001). Число лиц с выраженностью боли 4 по ЧРШ через 48 нед после перелома ЛК, травмы области КС и связок ГС составило 21,0, 16,9 и 11,9%, с умеренным или выраженным нарушением функции травмированной конечности 40,4, 26,2 и 16,3% соответственно. Потребность в приеме НПВП до 7 дней отмечена у 43,3%, 714 дней у 41,8%, более 2 нед или постоянно у 14,9% пациентов. Слабые или умеренно выраженные НР НПВП отмечены у 20,8% пациентов, в основном диспепсия и артериальная гипертензия. Отмена НПВП из-за НР потребовалась лишь у 2,6% пациентов. Сохранение боли 4 по ЧРШ ассоциировалось с исходно выраженной болью (7 по ЧРШ) отношение шансов 2,75 (95% доверительный интервал 0,834,13; p0,001) и наличием коморбидного остеоартрита КС и/или тазобедренного сустава отношение шансов 1,56 (95% доверительный интервал 1,032,34; р=0,039). Заключение. ПТБ быстро снижается у большинства пациентов после перелома ЛК, травмы области КС и связок ГС на фоне приема оригинального мелоксикама. Тем не менее у существенной части пациентов умеренная или выраженная ПТБ сохраняется через 48 нед, что требует пролонгированной обезболивающей терапии и активной реабилитации.

Topics: Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Male; Meloxicam; Middle Aged; Outpatients; Pain; Raptors

Topics: Administration, Intravenous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Humans; Meloxicam; Pain

An extended-release formulation of the NSAID meloxicam (MSR) is used to provide 72 h of continuous analgesia in many species, including rodents. Although standard formulations of meloxicam are frequently used in rats with no observable injection-site reactions, the potential adverse effects from MSR have not been characterized sufficiently nor has a prospective study of these effects been performed in rats. To address this deficiency, we evaluated injection-site reactions after a single subcutaneous administration of MSR (

Topics: Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Female; Male; Meloxicam; Pain; Prospective Studies; Rats; Rats, Sprague-Dawley

Topics: Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Buttocks; Diagnosis, Differential; Femur Head; Humans; Ilium; Magnetic Resonance Imaging; Male; Meloxicam; Osteomyelitis; Pain; Physical Examination; Pubic Bone; Soccer

In humans, pain due to osteoarthritis has been demonstrated to be associated with insomnia and sleep disturbances that affect perception of pain, productivity, and quality of life. Dogs, which develop spontaneous osteoarthritis and represent an increasingly used model for human osteoarthritis, would be expected to show similar sleep disturbances. Further, these sleep disturbances should be mitigated by analgesic therapy. Previous efforts to quantify sleep in osteoarthritic dogs using accelerometry have not demonstrated a beneficial effect of analgesic therapy; this is despite owner-reported improvements in dogs' sleep quality. However, analytic techniques for time-series accelerometry data have advanced with the development of functional linear modeling. Our aim was to apply functional linear modeling to accelerometry data from osteoarthritic dogs participating in a cross-over non-steroidal anti-inflammatory (meloxicam) drug trial. Significant differences in activity patterns were seen dogs receiving drug (meloxicam) vs. placebo, suggestive of improved nighttime resting (sleep) and increased daytime activity. These results align with owner-reported outcome assessments of sleep quality and further support dogs as an important translational model with benefits for both veterinary and human health.

Topics: Analgesics; Animals; Dog Diseases; Dogs; Female; Humans; Male; Meloxicam; Osteoarthritis; Pain; Sleep; Sleep Initiation and Maintenance Disorders

The aim of this work was to study the influence of solidification of meloxicam (Mel) containing nanosuspension (nanoMel) on the physical stability and drug bioavailability of the products. The nanoMel sample had poly(vinyl alcohol) (PVA) as a protective polymer, but no surfactant as a further stabilizing agent because the final aim was to produce surfactant-free solid phase products as well.. The solidified samples produced by fluidization and lyophilization (fluidMel, lyoMel) were examined for particle size, crystallinity, and in vitro release of Mel compared to similar parameters of nanoMel. The products were subjected to an animal experiment using per oral administration to verify their bioavailability.. Mel containing (1%) nanoMel sample was produced by wet milling process using an optimized amount of PVA (0.5%) which resulted in 130 nm as mean particle size and a significant reduction in the degree of crystallinity (13.43%) of Mel. The fluidization technique using microcrystalline cellulose (MCC) as carrier resulted in a quick conversion and no significant change in the critical product parameters. The process of lyophilization required a longer operation time, which resulted in the amorphization of the crystalline carrier (trehalose) and the recrystallization of Mel increased its particle size and crystallinity. The fluidMel and lyoMel samples had nearly five-fold higher relative bioavailability than nanoMel application by oral administration. The correlation between in vitro and in vivo studies showed that the fixed Mel nanoparticles on the surface of solid carriers (MCC, trehalose) in both the artificial gastric juice and the stomach of the animals rapidly reached saturation concentration leading to faster dissolution and rapid absorption.. The solidification of the nanosuspension not only increased the stability of the Mel nanoparticles but also allowed the preparation of surfactant-free compositions with excellent bioavailability which may be an important consideration for certain groups of patients to achieve rapid analgesia.

Topics: Administration, Oral; Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Cyclooxygenase 2 Inhibitors; Drug Liberation; Drug Stability; Humans; Meloxicam; Nanoparticles; Pain; Particle Size; Polyvinyl Alcohol; Surface Properties; Suspensions

Damage to periarticular soft tissues is a common pathology that causes severe pain and impaired function of the musculoskeletal system.. To determine the frequency, nature and clinical features of damage to periarticular soft tissues in real clinical practice, as well as the effectiveness of non - steroidal anti - inflammatory drugs (NSAIDs) in the debut of treatment of this pathology.. During the observational study, the frequency of defeat of the periarticular soft tissues in the structure of visits to 68 outpatient orthopedic surgeons in different cities of Russia for 1 month was estimated. Assessed the nature and dynamics of clinical manifestations during treatment in 1227 patients with defeat of the periarticular soft tissues. NSAIDs, mainly the original meloxicam, were used as a "first line" treatment for damage of the periarticular soft tissues. The results of treatment were evaluated after 10-14 days at a repeat visit of patients.. The proportion of patients with damage of the periarticular soft tissues was 15.8% of the total number of people who applied for outpatient care. Among 1227 patients (men 57.5%, average age 51.3±15.5 years) who were observed in the dynamics, prevailed were those with damage of the periarticular soft tissues of the knee joint area (knee joint enthesopathy, prepatellar bursitis, tendonitis/ bursitis of the goose foot area) - 21.2%, feet (plantar fasciitis, calcaneal spur) - 16.9%, shoulder (tendonitis of the muscles of the shoulder rotators) - 16.4% and the elbow (lateral and medial epicondylitis) - 15.3%. During treatment, there was a significant decrease in the total severity of pain - from 6.58±1.61 to 2.48±1.60 points on an 11-point numerical rating scale (p.. Поражение околосуставных мягких тканей в реальной клинической практике: частота, характер, эффективность нестероидных противовоспалительных препаратов Цель исследования. Определить частоту, характер и клинические особенности ПОМТ в реальной клинической практике, а также эффективность нестероидных противовоспалительных препаратов (НПВП) в дебюте лечения этой патологии. Материалы и методы. В ходе наблюдательного исследования оценивалась частота ПОМТ в структуре обращений к 68 амбулаторным хирургам - ортопедам в разных городах России в течение 1 мес. Проведена оценка характера и динамики клинических проявлений в ходе лечения у 1227 пациентов с ПОМТ. В качестве средства «первой линии» для лечения ПОМТ использовались НПВП, в основном оригинальный мелоксикам. Результаты лечения оценивались через 10-14 дней при повторном визите пациентов. Результаты. Доля пациентов с ПОМТ составила 15,8% от общего числа лиц, обращавшихся за амбулаторной помощью. Среди 1227 больных (мужчин 57,5%, средний возраст 51,3±15,5 года), которые наблюдались в динамике, преобладали лица с ПОМТ области коленного сустава (энтезопатия коленного сустава, препателлярный бурсит, тендинит/бурсит области «гусиной лапки») - 21,2%, стопы (плантарный фасциит, «пяточная шпора») - 16,9%, плеча (тендинит мышц ротаторов плеча) - 16,4% и локтя (латеральный и медиальный эпикондилит) - 15,3%. На фоне лечения отмечалось существенное уменьшение суммарной выраженности боли - с 6,58±1,61 до 2,48±1,60 балла по 11-балльной числовой рейтинговой шкале (p.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Humans; Knee Injuries; Knee Joint; Male; Meloxicam; Middle Aged; Pain; Russia; Soft Tissue Injuries

Research investigating the pain of normal parturition is lacking as there are few objective methods for measuring pain. The objective of this research was to describe the gait of cows following eutocia using pressure mat gait analysis; and if meloxicam alters the gait of cows. Twenty Holstein cows within 26 h of unassisted calving were enrolled into the study. Treatment groups included: 1) postpartum cows administered meloxicam (MEL; n = 10); and 2) postpartum cows administered placebo (PLBO; n = 10). Meloxicam was administered by oral bolus at 1 mg/kg within 26 h of calving. Placebo cows were given an oral bolus of dry whey powder within 26 h of calving. A commercially available floor mat-based pressure/force measurement system was used to compare ambulation between treatment groups. Cows were walked across the mat before treatment administration, and 2, 4, 6, 8, 12, 24, 48, and 72 h posttreatment. The percent of total force, percent total contact pressure, and percent total impulse of the rear limbs were calculated. Outcome measures were statistically analyzed using repeated measures, with the cow serving as the experimental unit. Cows in the MEL group placed 48.9% (95% CI: 47.4% to 50.5%) of total force on the rear limbs compared to 46.3% (95% CI: 44.7% to 47.9%) in PLBO cows (P = 0.02). Total impulse on their rear limbs for the MEL cows was 50.5% (95% CI: 48.6% to 52.4%) compared to 46.7% (95% CI: 44.8% to 48.7%) for the PLBO cows (P = 0.01). No differences in contact pressure of the rear limbs were observed (P = 0.27). The PLBO cows had a longer gait 101.3 cm (95% CI: 95.9% to 106.6 cm) vs. 90.8 cm (95% CI: 85.4% to 96.1 cm) (P = 0.03). These findings show meloxicam-treated cows have altered weight distribution to the rear limbs as measured by pressure mat gait analysis, suggesting meloxicam may effectively treat postpartum pain.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Female; Gait; Gait Analysis; Lactation; Meloxicam; Pain; Pain Measurement; Parturition; Postpartum Period; Pressure; Walking

Can pain be objectively assessed in macaques with naturally occurring endometriosis?. Behavioral, pharmacological and in vivo brain imaging findings indicate that pain can be quantified in macaques with endometriosis.. Endometriosis is characterized by abdominopelvic hypersensitity. The mechanism by which endometriosis evokes pain is largely unknown, as currently available analgesics offer limited pain relief. Thus, there is a need for both greater understanding of the in vivo mechanism of endometriosis-associated pain and better methods of testing novel therapeutics.. Pain-related behavior and brain activation were assessed in five cynomolgus macaques with endometriosis. Three healthy female macaques served as controls.. Abdominopelvic sensitivity to force was assessed with an algometer. Activation of brain areas using block design force stimulation and the effects of a single dose of the analgesic drug morphine and 2-month treatment with the progestin dienogest on brain activation were observed via functional magnetic resonance imaging.. Pain response thresholds in macaques with endometriosis were significantly less than that of healthy macaques (P = 0.0003). In addition, non-noxious force activated the insula and thalamus, which was reduced with morphine and 2-month dienogest treatment.. The specific role of cysts, such as peritoneal cysts, in endometriosis pain was not explored. While non-noxious stimulation activated the insula and thalamus, macaques were sedated during fMRI scans. Current findings need further confirmation in a larger cohort.. The current study demonstrated central sensitization and related pain behavior in macaques with naturally occurring endometriosis. Altered functioning of the central nervous system could be the focus of future mechanistic studies and for the development of novel therapeutics.. Supported by a grant from the Shizuoka Industrial Foundation. All authors are employees of Hamamatsu Pharma Research, Inc.

Topics: Acetaminophen; Analgesics; Animals; Behavior, Animal; Brain; Central Nervous System; Endometriosis; Female; Macaca fascicularis; Magnetic Resonance Imaging; Meloxicam; Morphine; Nandrolone; Pain

Topics: Animals; Australia; Buffaloes; Dogs; Health Education; Internet; Jejunum; Lymphoma; Meloxicam; Pain; Poultry; Sheep

Assisted calves are often born weak, injured, or oxygen deprived and have a higher risk of morbidity and mortality. The objective was to investigate the impact of using pain mitigation at birth in assisted beef calves on physiological indicators of pain and inflammation, passive immunity, health, and growth. Thirty-three primiparous cows and their calves requiring assistance at birth on two ranches located in southern Alberta were enrolled. Data collected at birth include date and time of calving, calf sex, meconium staining, presentation of calf, and calving difficulty (easy assist: one person manually delivered the calf; difficult assist: delivery by two or more people, or mechanical assistance). Within 10 min of birth, calves were stratified by calving difficulty, randomized to a medication group, and received a subcutaneous dose of meloxicam (0.5 mg/kg BW) or an equivalent volume of placebo. Cow-calf pairs were then placed in individual box stalls for observation and sampling. At birth, 1, 4, and 24 h after birth, heart rate, respiratory rate, and rectal temperature were assessed and blood samples collected to measure indicators of pain and inflammation (cortisol, corticosterone, substance P, and haptoglobin). Serum IgG concentration and failed transfer of passive immunity (serum IgG concentration <24 g/L) were assessed in the 24-h blood samples. Preweaning treatment for disease and mortality information was collected and calves were weighed at 7 to 10 d of age and at weaning. Of the 33 calves enrolled, 17 calves received meloxicam and 16 calves received a placebo. Meloxicam-medicated calves had significantly greater ADG to 7 to 10 d of age (P = 0.05) (mean = 0.9 kg/d; SE = 0.10) compared with placebo-medicated calves (mean = 0.6 kg/d; SE = 0.12). There was no significant effect of meloxicam on physiological indicators of pain and inflammation, standing or nursing by 1 h, passive immunity, health outcomes, or ADG to weaning (P > 0.1). Although this was a small sample population, meloxicam given to assisted calves at birth improved ADG in the first week of life, which may indicate an important production management tool for improving well-being in assisted calves.

Topics: Alberta; Animal Husbandry; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Female; Haptoglobins; Inflammation; Male; Meloxicam; Pain; Parturition; Pregnancy; Weaning

Flystrike costs the Australian industry $173 to 280 M per annum and 70% to 80% of Merino lambs are currently mulesed to reduce the risk of flystrike. To alleviate welfare concerns there has been widespread adoption of analgesics to mitigate the pain associated with mulesing. The objective of this experiment was to determine the effectiveness of Tri-Solfen® and meloxicam (Metacam® 20) at reducing pain-related behavioural responses to mulesing in Merino lambs. One hundred and forty Merino lambs were allocated to one of seven treatment groups: (1) non-mulesed (Control); (2) mulesed with no pain relief; (3) subcutaneous (s.c.) meloxicam administered 15 min before mulesing; (4) Tri-Solfen® administered at time of mulesing; (5) Tri-Solfen® and saline injection (s.c.) 15 min before mulesing; (6) Tri-Solfen® and meloxicam (s.c.) 15 min before mulesing; and (7) meloxicam (s.c.) at time the of mulesing. Behavioural responses such as standing, walking and lying were measured every 15 min for 6 h on the day of marking and for up to 2 h for 4 days thereafter. Standing (hunched v. normal) and walking (stiff v. normal) behaviours were then categorised into pain- and normal-related behaviours while lying remained in its own category. Mulesed lambs with no pain relief displayed significantly more pain-related behaviours than Control lambs during the 6 h post-mulesing (1.22 v. 0.22 out of a total score of 3; RSD=1.15). Lambs that received a combination of pain relief displayed significantly less pain-related behaviour than mulesed lambs with no pain relief on the day of mulesing (0.85 v. 1.22 out of a total score of 3; RSD=1.15). Administration of meloxicam or Tri-Solfen® on their own had minimal if any significant effect on pain-related behaviours on the day of mulesing. The results of this experiment support the use of pain-related behaviours to measure the efficacy of analgesics and the use of multimodal analgesia during mulesing of lambs.

Topics: Analgesics; Animal Welfare; Animals; Anti-Infective Agents, Local; Anti-Inflammatory Agents, Non-Steroidal; Australia; Behavior, Animal; Drug Combinations; Female; Injections, Subcutaneous; Male; Meloxicam; Orchiectomy; Pain; Sheep; Sheep Diseases; Sheep, Domestic

To evaluate the effects of the nutraceuticals omega-6/3 and omega-9/6 on endometriosis-associated infertility and pain.. Controlled experimental study, with each group composed of eight female rats. Fertility groups: sham-operated control (0.9% saline solution); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); and meloxicam (0.8 mg/kg/day). Pain groups: sham-operated control (0.9% saline); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); medroxyprogesterone acetate (5 mg/kg/every 3 days); and meloxicam (0.8 mg/kg/day). Peritoneal endometriosis was surgically induced. Pain was evaluated with the writhing test. Fertility was evaluated by counting the number of embryos in the left hemi-uterus.. The mean number of writhings was as follows: sham-operated, 11.1 ± 2.9; control with endometriosis, 49.3 ± 4.4; omega-6/3, 31.5 ± 2.7; omega-9/6, 34.1 ± 4.5; medroxyprogesterone acetate, 2.1 ± 0.8; meloxicam, 1 ± 0.3. There was a significant difference between both controls and all drugs used for treatment. Regarding fertility, the mean values were as follows: sham-operated, 6.8 ± 0.6; control with endometriosis, 4.2 ± 0.7; omega-6/3, 4.7 ± 1; omega-9/6, 3.8 ± 0.9; and meloxicam, 1.8 ± 0.9.. The omega-6/3 and omega-9/6 nutraceuticals decreased pain compared to the controls. There was no improvement in fertility in any of the tested groups.

Topics: Animals; Disease Models, Animal; Endometriosis; Fatty Acids, Omega-3; Female; Fertility; Medroxyprogesterone Acetate; Meloxicam; Pain; Peritoneum; Rats

Oral meloxicam is labelled for reducing pain and inflammation associated with castration in cattle in Canada, however, subcutaneous meloxicam is only labelled for pain associated with dis-budding and abdominal surgery. The aim of this project was to determine the pharmacokinetic profile of oral (PO; 1.0 mg/kg BW) and subcutaneous meloxicam (SC; 0.5 mg/kg BW), and to assess the effect of meloxicam on physiological and behavioural indicators of pain associated with knife castration in 7-8 month old calves. Twenty-three Angus crossbred beef calves (328 ± 4.4 kg BW) were randomly assigned to two treatments: PO n = 12 or SC n = 11 administration of meloxicam immediately before knife castration. Physiological parameters included salivary and hair cortisol, substance P, haptoglobin, serum amyloid-A, weight, complete blood count, scrotal and rectal temperature. Behavioural parameters included standing and lying behaviour, pen behaviour and feeding behaviour. Data were analyzed using PROC GLIMMIX (SAS), with repeated measures using mixed procedures including treatment as a fixed effect and animal and pen as a random effect. The pharmacokinetic profile of the drug including area under the curve, volume of distribution and clearance was greater (P < 0.05) in PO than SC calves. After surgery, substance P concentrations, white blood cell counts (WBC), weight and lying duration were greater (P < 0.05) in PO than SC calves, while scrotal circumference was lower (P < 0.05) in PO calves than SC calves. Although statistical differences were observed for pharmacokinetic, physiological and behavioural parameters differences were small and may lack biological relevance.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Inflammation; Injections, Subcutaneous; Male; Meloxicam; Orchiectomy; Pain

Nonsteroidal anti-inflammatory drugs such as flunixin meglumine have been used to treat signs of systemic inflammatory conditions, but it is also known to have the side effect to small intestine mucosa. It may be considered to be due to inhibition of both cyclooxygenase (COX)-1 and COX-2. On the other hand, meloxicam is widely used in equine clinical practice and an effective nonsteroidal anti-inflammatory drug with the preferential inhibitory effect on COX-2. However, it has not yet been evaluated in equine systemic inflammation. The aim of this study was to evaluate the effect of meloxicam administered 60 minutes prior lipopolysaccharide (LPS)-induced inflammatory response in five Thoroughbred horses using a crossover test. Clinical parameters including body temperature, heart rate, respiratory rate, behavioral pain score, and hoof wall surface temperature were recorded, and plasma tumor necrosis factor-alpha, cortisol, and leukocyte counts were measured at various times before and after LPS infusion for 420 minutes. At time points 60, 90 (P < .01), 120, and 180 (P < .05) minutes, pain scores were significantly lower in meloxicam-treated horses. There was no significant difference in other parameters. In the present study, we revealed the analgesic effect of meloxicam using an equine low-dose endotoxin model.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Endotoxins; Horses; Meloxicam; Pain

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline (1 ml/kg). Tumours were imaged and welfare was assessed using body weight, behaviour and nociceptive responses. In study 1, BALB/c mice were inoculated with 4T1 mammary carcinoma or saline during surgery or anaesthesia. As pre-treatment with a single buprenorphine dose appeared beneficial to cancer growth consistency, a second cohort of mice additionally received saline or buprenorphine at 12 and 24 h. Surgery resulted in increased mammary tumour growth and lung metastases. These unwanted effects were lessened by buprenorphine pre-treatment, especially when given repeatedly. Mammary tumour-bearing mice became less active and nociceptive thresholds declined over time, indicating some discomfort as tumours grew. In study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to determine whether meloxicam or buprenorphine affected cancer seeding of the lungs. While meloxicam reduced B16 lung seeding, buprenorphine did not. Mechanical thresholds decreased as cancer developed in mice bearing melanoma, but the magnitude of this was insufficient to conclude that there were any significant welfare concerns. This study highlights the scientific value in utilising non-surgical models, where possible. When surgery must be performed at the time of tumour inoculation, the effects of this should be controlled with appropriate analgesics to enhance the value and possibly translation of the research.

Topics: Analgesics; Animal Welfare; Animals; Breast Neoplasms; Buprenorphine; Cell Line, Tumor; Disease Models, Animal; Female; Lung Neoplasms; Mammary Neoplasms, Experimental; Melanoma, Experimental; Meloxicam; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Pain; Thiazines; Thiazoles; Xenograft Model Antitumor Assays

Our objective was to determine the effect of castration timing, method, and use of the analgesic meloxicam (MEL) on inflammation, behavior, performance, and carcass traits in feedlot cattle. This study was a randomized complete block design conducted over a 3-yr period. In total, 194 crossbred beef calves from a single ranch origin were randomized at birth to receive one of five treatments arranged as a 2 × 2 + 1 factorial: 1) bulls castrated within 48 h of birth (CON), 2) bulls surgically castrated on day 0 without MEL (SUR), 3) bulls surgically castrated on day 0 with MEL (SUR + MEL), 4) bulls band castrated on d 0 without MEL (BAN), and 5) bulls band castrated on day 0 with MEL (BAN + MEL). Upon feedlot arrival (day -11; average 287 ± 2.03 d of age), animals were blocked by initial BW (224 ± 4.5 kg) and assigned randomly to treatment pens in three consecutive years (n = 2 pens per treatment in each year). Oral MEL was administered at 1 mg/kg BW concurrent with applicable castration treatment on day 0. Data were analyzed using the MIXED and GLIMMIX procedures of SAS with pen (year) serving as experimental unit. From days 0 to 7, ADG was reduced (P = 0.01) for surgical (-0.42) compared to band (0.43 kg/d) castration. Conversely, ADG was increased for surgical (1.74) vs. band (1.46 kg/d) castration from days 14 to 32. There was also an overall (day 0 to final) improvement in ADG for MEL (P = 0.02), but no effect of castration method was observed (P = 0.81). The CON group had the greatest (P = 0.05) marbling score. Backfat thickness was increased (P = 0.01) for MEL. A treatment × day interaction (P = 0.04) existed for serum haptoglobin, with SUR having the greatest (P < 0.01) concentration on days 1 and 4. Meloxicam administered in the surgically castrated treatment reduced (P = 0.01) serum haptoglobin concentration on day 1. Relative to baseline, standing duration for surgical castration was increased 113 min (P < 0.01), while banding caused 6.7 more lying bouts (P < 0.01) immediately following castration on day 0. Step count was greatest for BAN, intermediate for CON, and least for surgical (P < 0.01). Results suggest that MEL mitigated the more pronounced inflammation observed for surgical castration, whereas behavior was differentially altered for castration method indicative of a divergent pain response. Castration, regardless of method, transiently reduced ADG, but MEL administration improved overall ADG for both methods.

Topics: Analgesia; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cattle; Haptoglobins; Inflammation; Male; Meloxicam; Orchiectomy; Pain; Pain Management; Random Allocation; Thiazines; Thiazoles

Although the pain caused by castration of calves is a significant animal welfare issue for the beef industry, analgesia is not always used for this procedure, largely because of practical limitations associated with injectable forms of pain relief. Novel analgesic formulations have now been developed for livestock to allow topical and buccal administration, offering practical options to improve cattle welfare if shown to be effective. To assess the effects of topical anaesthetic (TA) and buccal meloxicam (BM) on average daily gain (ADG), behaviour and inflammation following surgical castration of beef calves, a total of 50 unweaned bull calves were randomly allocated to: (1) sham castration (SHAM, n=10); (2) surgical castration (C, n=10); (3) surgical castration with pre-operative buccal meloxicam (CBM, n=10); (4) surgical castration with post-operative topical anaesthetic (CTA, n=10); and (5) surgical castration with pre-operative buccal meloxicam and post-operative topical anaesthetic (CBMTA, n=10). Calves were recorded on video for 5 h following treatment and the frequency and duration of specific behaviours displayed by each animal was later observed for 5 min every hour (total of 25 min). Average daily gain was calculated 1, 2 and 6 days following treatment. Scrotal diameter measurements and photographs of wounds were collected from all castrated calves 1, 2 and 6 days following treatment to evaluate inflammation and wound healing. Infrared photographs were used to identify maximum scrotal temperature. Digital photographs were used to visually score wounds on a numerical rating scale of 1 to 5, with signs of inflammation increasing and signs of healing decreasing with progressive scores. Sham castration calves displayed significantly less, and C calves displayed significantly more foot stamps than all other calves (P=0.005). Observations on the duration of time that calves displayed a hypometric 'stiff gait' locomotion, indicated that SHAM calves tended to spend no time, C calves tended to spend the greatest time and all other calves tended to spend an intermediate time displaying this behaviour (P=0.06). Maximum scrotal temperatures were lower in CBM and CBMTA calves than C and CTA calves 2 days following treatment (P=0.004). There was no significant effect of treatment on ADG (P=0.7), scrotal diameter (P=0.09) or wound morphology score (P=0.5). These results suggest that TA and BM, alone or in combination, reduced pain and BM reduced inflammation f

Topics: Analgesics; Anesthesia, Local; Anesthetics, Local; Animal Welfare; Animals; Behavior, Animal; Cattle; Inflammation; Male; Meloxicam; Orchiectomy; Pain; Random Allocation

Migraine is the third most common disease in the world (behind dental caries and tension-type headache) with an estimated global prevalence of 15%, yet its etiology remains poorly understood. Recent clinical trials have heralded the potential of therapeutic antibodies that block the actions of the neuropeptide calcitonin gene-related peptide (CGRP) or its receptor to prevent migraine. Calcitonin gene-related peptide is believed to contribute to trigeminal nerve hypersensitivity and photosensitivity in migraine, but a direct role in pain associated with migraine has not been established. In this study, we report that peripherally administered CGRP can act in a light-independent manner to produce spontaneous pain in mice that is manifested as a facial grimace. As an objective validation of the orbital tightening action unit of the grimace response, we developed a squint assay using a video-based measurement of the eyelid fissure, which confirmed a significant squint response after CGRP injection, both in complete darkness and very bright light. These indicators of discomfort were completely blocked by preadministration of a monoclonal anti-CGRP-blocking antibody. However, the nonsteroidal anti-inflammatory drug meloxicam failed to block the effect of CGRP. Interestingly, an apparent sex-specific response to treatment was observed with the antimigraine drug sumatriptan partially blocking the CGRP response in male, but not female mice. These results demonstrate that CGRP can induce spontaneous pain, even in the absence of light, and that the squint response provides an objective biomarker for CGRP-induced pain that is translatable to humans.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies; Calcitonin Gene-Related Peptide; Disease Models, Animal; Facial Pain; Injections, Intraperitoneal; Locomotion; Meloxicam; Mice; Mice, Inbred C57BL; Pain; Serotonin 5-HT1 Receptor Agonists; Sumatriptan

Painful neuropathic injuries are accompanied by robust inflammatory and oxidative stress responses that contribute to the development and maintenance of pain. After neural trauma the inflammatory enzyme cyclooxygenase-2 (COX-2) increases concurrent with pain onset. Although pre-treatment with the COX-2 inhibitor, meloxicam, before a painful nerve root compression prevents the development of pain, the pathophysiological mechanisms are unknown. This study evaluated if pre-treatment with meloxicam prior to painful root injury prevents pain by reducing spinal inflammation and peripheral oxidative stress. Glial activation and expression of the inflammatory mediator secreted phospholipase A

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Astrocytes; Cervical Cord; Disease Models, Animal; Ganglia, Spinal; Inflammation; Male; Meloxicam; Microglia; Neurons; Oxidative Stress; Pain; Peripheral Nervous System Diseases; Radiculopathy; Rats, Sprague-Dawley; Spinal Nerve Roots

The aim of this study was to evaluate the effect of a single dose of subcutaneous (s.c.) meloxicam administered at the time of knife and band castration on inflammatory response and wound healing over 56-d post-castration. Seventy-two Angus crossbred calves (47.3 ± 6.70 kg of body weight [BW] and 7 to 8 d of age) were randomly assigned according to a 3 × 2 factorial design assessing castration method: sham (CT), band (BA), and knife (KN) castration, and pain mitigation: non-medicated (NM) and medicated calves (M) injected s.c. with meloxicam (0.5 mg/kg of BW). Calf BW, rectal temperature, swelling ("0": no swelling; "4": swelling needing intervention) and healing score ("1" to "5" with "5" being completely healed), scrotal circumference, and maximum scrotal temperature were measured on d -1, immediately before castration (d 0), and weekly thereafter over a 56-d period. Blood samples for haptoglobin (Hp), serum amyloid-A (SAA), and complete blood cell count were collected according to the same schedule. Hair samples were collected on d -1, 28, and 56 to determine cortisol concentrations. Standing and lying behaviors were measured using accelerometers that were placed on the calves on d -1 until d 35, and visual observations of behaviors related to pain were recorded once a week for 35 d. Knife-castrated calves achieved swelling scores of "3" and "2" between d 7 and 14, which was sooner (Z< 0.05) than in BA calves (from d 14 to 35). In addition, greater (P = 0.03) concentrations of SAA were observed in BA calves (76.9 ± 0.12 g/liter) compared with CT (57.6 ± 0.12 g/liter) and KN (51.6 ± 0.12 g/liter) from d 7 to 35. Healing scores of "2" and "4" tended to be achieved sooner (Z < 0.10) in KN calves than in BA calves, although healing scores of "3" tended to be achieved sooner (Z < 0.10) in BA calves than KN calves. No differences (P > 0.10) were observed among treatments for hair cortisol on d -1 and 28, but on d 56, hair cortisol concentrations in BA-NM calves were greater (P > 0.05) than for CT-NM, BA-M, KN-NM, and KN-M, and tended to be greater (P = 0.08) than for CT-M calves. Lying duration tended (P = 0.10) to be greater and suckling behavior tended (P = 0.08) to be lower in NM than M calves. A single s.c. injection of meloxicam did not reduce long-term inflammatory responses or improve wound healing; however, it may be useful in reducing pain and stress in band castrated calves as evidenced by reduced hair cortisol concentrations up to 56 d post-castra

Topics: Animals; Body Weight; Cattle; Hair; Haptoglobins; Hydrocortisone; Male; Meloxicam; Orchiectomy; Pain; Pain Measurement; Random Allocation; Wound Healing

Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.. PEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam.. The present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Topics: Administration, Oral; Amides; Animals; Anti-Inflammatory Agents; Carrageenan; Drug Combinations; Edema; Ethanolamines; Hyperalgesia; Inflammation; Male; Meloxicam; Osteoarthritis; Pain; Palmitic Acids; Quercetin; Rats, Sprague-Dawley; Thiazines; Thiazoles

The present study was designed to examine the antinociceptive and anti-inflammatory effects of 7-chloro-4-phenylsulfonyl quinoline (PSOQ). Mice were orally (p.o) pretreated with PSOQ (0.01-10 mg/kg), meloxicam (10 mg/kg), 30 min prior to the acetic acid, hot-plate and open field tests. PSOQ reduced abdominal writhing induced by acetic acid, while meloxicam presented no effect. The latency time in the hot-plate test and locomotor/exploratory activities in the open field test were not altered by treatments. In order to evaluate the gastric tolerability after oral administration of PSOQ or meloxicam (10 mg/kg), mice were fasted for 18 h prior to drug exposure. Four hours later, the development of lesions was assessed. PSOQ and meloxicam did not induce ulcer at the dose and time evaluated. Indeed, anti-inflammatory and anti-edematogenic properties of PSOQ were investigated. For this, animals were pretreated with PSOQ (0.01-50 mg/kg; p.o.), meloxicam (50 mg/kg; p.o.), 30 min prior to croton oil application. PSOQ and meloxicam (50 mg/kg) diminished the edema formation and myeloperoxidase activity induced by croton oil in the ear tissue. Taken together these data demonstrated that PSOQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Croton Oil; Edema; Hot Temperature; Humans; Male; Meloxicam; Mice; Nociception; Pain; Quinolines; Stomach Ulcer; Thiazines; Thiazoles

The newly revised Canadian Codes of Practice for the management of beef cattle requires that as of 2018, calves older than 6 mo of age be castrated using pain control. Castration is a husbandry procedure commonly done without pain control, and there is a lack of agreement on an effective pain mitigation strategy specific to castration. The aim of this study was to identify the optimal time of administration of meloxicam prior to castration. Thirty-four Angus and Angus crossbred bull calves (282 ± 28.0 kg BW) were randomly assigned to 1 of 3 treatments receiving a single s.c. injection of meloxicam (0.5 mg/kg BW): 6 h (6H; = 11), 3 h (3H; = 12), or immediately (0H; = 11) before knife castration. Measurements included visual analog scale (VAS), head movement (HM), accelerometer movement (AM) and strain gauge exertion force (EF) on the squeeze chute, stride length (SL), lying and standing behavior, salivary cortisol (SC), haptoglobin, serum amyloid A (SAA), substance P (SP), and scrotal temperature (ST). Samples were collected on d -7, -5, -2, -1, and immediately before castration (T0) and 30, 60, 120, and 240 min and 1, 2, 5, 7, 14, 21, and 28 d after castration, except for VAS, AM, EF, and HM, which were obtained at the time of castration. A time × treatment effect ( = 0.01) was observed for SP, where 0H had lower concentrations than 3H and 6H calves 1 d after castration, whereas 3H calves tended to have greater levels than 6H calves 5 d after castration. Mean ST was greater ( < 0.01) in 6H calves compared to 0H and 3H calves 120 min after castration, whereas 6H and 3H calves had greater ST compared to 0H calves 240 min after castration. On d 1 after castration, 6H calves had greater ST than 0H and 3H calves, whereas 0H calves had greater ST compared to 3H and 6H calves on d 28 after castration. The SL tended ( = 0.09) to be shorter in 3H and 6H calves than 0H calves 30, 60, 120, and 240 min after castration. Number of peaks from the AM between 2 and 3 SD above or below the mean were greater ( = 0.03) in 3H and 6H calves than in 0H calves. No treatment differences ( > 0.10) were observed for the number of peaks and area for AM and EF, VAS, HM, SC, or haptoglobin. On the basis of these results, the optimal time to administer s.c. meloxicam in 7- to 8-mo-old knife-castrated calves is immediately before castration (0H), as evidenced by fewer indicators of pain and inflammation compared to 3H and 6H calves.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Canada; Cattle; Female; Haptoglobins; Hydrocortisone; Inflammation; Injections; Male; Meloxicam; Orchiectomy; Pain; Random Allocation; Substance P; Thiazines; Thiazoles; Weaning

The objectives of this study were to describe the routine use of analgesics by Ontario veterinarians for common surgeries in dogs and cats, and to compare routine use of analgesics between species and surgeries, using Chi-square analyses. In total, 239 veterinarians responded to the questionnaires; a response rate of 13.1%. Fifty-two percent to 79% of veterinarians used meloxicam for both species and all surgeries. Approximately 9% of veterinarians did not use analgesics for dog ovariohysterectomy and castration, while 16% to 22% did not use analgesics for these surgeries in cats. Veterinarians used and dispensed analgesics to dogs more often than to cats (

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Castration; Cats; Dogs; Female; Hysterectomy; Male; Meloxicam; Ontario; Ovariectomy; Pain; Pain, Postoperative; Surveys and Questionnaires; Thiazines; Thiazoles; Veterinarians

The efficacy of oral phenylbutazone [PBZ; 4.4 mg/kg body weight (BW), q12h], a non-selective non-steroidal anti-inflammatory drug (NSAID), and oral meloxicam (MXM; 0.6 mg/kg BW, q24h), a COX-2 selective NSAID, were evaluated in 2 experimental pain models in horses: the adjustable heart bar shoe (HBS) model, primarily representative of mechanical pain, and the lipopolysaccharide-induced synovitis (SYN) model, primarily representative of inflammatory pain. In the HBS model, PBZ reduced multiple indicators of pain compared with the placebo and MXM. Meloxicam did not reduce indicators of pain relative to the placebo. In the SYN model, MXM and PBZ reduced increases in carpal skin temperature compared to the placebo. Meloxicam reduced lameness scores and lameness-induced changes in head movement compared to the placebo and PBZ. Phenylbutazone reduced lameness-induced change in head movement compared to the placebo. Overall, PBZ was more effective than MXM at reducing pain in the HBS model, while MXM was more effective at reducing pain in the SYN model at the oral doses used.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Horses; Lameness, Animal; Lipopolysaccharides; Male; Meloxicam; Pain; Phenylbutazone; Skin Temperature; Synovitis; Thiazines; Thiazoles; Treatment Outcome

Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Kidney; Kidney Diseases; Liver; Meloxicam; Metaplasia; Pain; Rats; Rats, Sprague-Dawley; Stomach; Stomach Diseases; Thiazines; Thiazoles; Toxicity Tests

An approximately 5-year-old female grey-headed parrot (Poicephalus fuscicollis suahelicus) was evaluated after exposure to outdoor temperatures below -20°C (-4°F) for approximately 22 hours. Severe frostbite affecting multiple digits, as well as dehydration and a depressed attitude, were diagnosed. Treatment included oral antibiotics, antifungals, nonsteroidal anti-inflammatories (NSAIDs), pentoxifylline, and topical aloe vera. Surgical amputation of the affected toes was not performed. Mild to moderate pododermatitis over the intertarsal joints developed because of a shift in weight bearing after the loss of most digits. Within 5 months after initial presentation, all frost-damaged toes had self-amputated, and the bird was able to function independently with no limitations in mobility.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Bird Diseases; Enrofloxacin; Female; Fluoroquinolones; Frostbite; Itraconazole; Meloxicam; Pain; Pentoxifylline; Psittaciformes; Thiazines; Thiazoles; Vasodilator Agents

Rodent grimace scales have been recently validated for pain assessment, allowing evaluation of facial expressions associated with pain. The standard scoring method is retrospective, limiting its application beyond pain research. This study aimed to assess if real-time application of the Rat Grimace Scale (RGS) could reliably and accurately assess pain in rats when compared to the standard method. Thirty-two male and female Sprague-Dawley rats were block randomized into three treatment groups: buprenorphine (0.03 mg/kg, subcutaneously), multimodal analgesia (buprenorphine [0.03 mg/kg] and meloxicam [2 mg/kg], subcutaneously), or saline, followed by intra-plantar carrageenan. Real-time observations (interval and point) were compared to the standard RGS method using concurrent video-recordings. Real-time interval observations reflected the results from the standard RGS method by successfully discriminating between analgesia and saline treatments. Real-time point observations showed poor discrimination between treatments. Real-time observations showed minimal bias (<0.1) and acceptable limits of agreement. These results indicate that applying the RGS in real-time through an interval scoring method is feasible and effective, allowing refinement of laboratory rat welfare through rapid identification of pain and early intervention.

Topics: Analgesia; Animal Welfare; Animals; Buprenorphine; Carrageenan; Computer Systems; Facial Expression; Feasibility Studies; Female; Male; Meloxicam; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Retrospective Studies; Thiazines; Thiazoles; Video Recording

Pain alleviation associated with castration of piglets is an important welfare issue. The present study compares the effect of different approaches and products suitable for farmer use, with the aim to alleviate pain due to castration in piglets. A randomized within-litter design, with 28 replicate litters, compared 7 treatments: handling () restraint of the piglet and manipulation of the scrotum, castration without pain relief (), 2 treatments (, ) with different concentrations of tetracaine (2 and 6%) applied topically 10 min before and immediately post-surgery, and 3 treatments with i.m. injection of different nonsteroidal anti-inflammatory drugs () 10 min prior to surgery (-meloxicam, -ketoprofen, -tolfenamic acid). Efficacy of pain relief was assessed during a 300 min period after castration by serum cortisol, behavior (walking, lying, suckling, in the nest, isolated and pain related: tremors, rubbing the rear, hunching, wagging of the tail), facial expression and scrotal skin pressure sensitivity. C pigs had greater serum cortisol concentration than all other groups at 60 min post-surgery ( < 0.001), while H pigs had lower concentrations than pigs given topical anesthesia ( < 0.001) though not injected analgesia. No treatment differences were significant at 180 min, but at 300 min cortisol concentration was greater in T2 and T6 piglets than those given NSAIDs ( = 0.03). These treatment differences were mirrored by the pressure sensitivity of the scrotum; in comparison with C piglets, those given NSAIDs showed a reduced sensitivity ( 0.003) but those given local anesthesia did not ( = 0.15). C pigs showed increased frequency of pain-related behavior in the first 30 min in comparison with all other treatments, more time isolated than H or NSAID treatments, and more time standing inactive than H or K treatments. No behavioral differences were apparent after 60 min. No differences in facial expressions were observed among treatments. In conclusion, on-farm methods for pain relief can provide some, though not complete, pain alleviation in the hours after castration. The use of topical anesthesia gave only minor benefit in comparison to NSAID agents injected prior to castration. Since the main differences in indicators of pain between positive and negative controls were observed within the first h after castration, it is important to select drugs that act quickly after administration to facilitate practical processing schedules on farm.

Topics: Anesthesia, Local; Animal Husbandry; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Hydrocortisone; Ketoprofen; Male; Meloxicam; Orchiectomy; ortho-Aminobenzoates; Pain; Pain Management; Swine; Thiazines; Thiazoles

Meloxicam (MLX) is a poorly water-soluble non steroidal anti-inflammatory drug (NSAID). The main objective of the present work was to enhance the dissolution of MLX and thus its bioavailability by the aid of additives. The novelty of this work rises from the utilization of spray drying technology to produce micro particulates solid dispersion systems containing MLX in the presence of small amount of additives. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and Scan Electron Microscope (SEM) were used for studying the physico-chemical and morphological properties of MLX samples. The dissolution of MLX samples was investigated in two different pH media. The morphology of MLX solid dispersion micro-particles was spherical in shape according to SEM. FT-IR profiles indicated that a complex was formed between MLX and the additives. DSC patterns of the MLX micro-particles suggested a reduction in the crystallinity of MLX and probability of presence of an interaction between MLX and the additives. The rate of dissolution of the spray-dried MLX enhanced as compared with the unprocessed MLX in both acidic and neutral media. It was found that 100% of the added MLX released within 5 min in phosphate buffer dissolution medium (pH 7.4) compared to that of the unprocessed MLX (15% in 60 min). Such increase rate in the dissolution of the spray dried MLX could be attributed to the increase in wettability of MLX particles and the hydrophilic nature of the additives. The anti-inflammatory effect of the spray dried MLX was explored using formalin induced rat paw edema model. The spray-dried samples showed an increase in the anti-inflammatory activity of MLX as compared to the unprocessed MLX. This work reveals that the spray drying technique is suitable for preparation of micro-particles with improved dissolution and anti-inflammatory effect of MLX.

Topics: Aerosols; Animals; Anti-Inflammatory Agents, Non-Steroidal; Buffers; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Crystallography, X-Ray; Desiccation; Disease Models, Animal; Excipients; Formaldehyde; Hydrogen-Ion Concentration; Kinetics; Male; Meloxicam; Microscopy, Electron, Scanning; Pain; Particle Size; Rats, Wistar; Solubility; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical; Thiazines; Thiazoles; Water

Nonsteroidal anti-inflammatory drugs (NSAIDs) are particularly used in patients with bone fractures, but there are limited studies on whether one NSAID is superior to another. In this study, we used histopathological and biochemical parameters to determine whether there are differences between the effects of the administration of clinical doses of dexketoprofen trometamol (DEXT), meloxicam (MEL) and diclofenac sodium (DIC) on the healing of closed fibular fractures and the toxicity of both the liver and kidney.. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups of seven each. Closed diaphyseal fractures were formed in the left fibulas of all of the rats. The NSAIDs dexketoprofen trometamol (DEXT) (Arveles(®)), meloxicam (MEL) (Melox(®)) and diclofenac sodium (DIC) (Voltaren(®)) were intramuscularly administered to Groups I, II, and III, respectively, for a period of 10 days after the fibular fractures were performed. No pharmacological agents were administered to Group IV (Control group). Blood samples were collected from all of the rats after the fractures were performed, and the rats were sacrificed on day 28. The histopathological findings were compared, and the blood samples were evaluated to determine any differences between the levels of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA).. Our results suggest that DEXT and MEL impair the healing of bone fractures and that DIC does not histopathologically affect the healing process of bone fractures. We also found that DEXT, MEL, and DIC impaired the renal histopathology compared with the control group. However, the liver histopathological analysis showed that DEXT and MEL caused a higher degree of parenchymal necrosis compared with DIC.. Based on our results, DIC can be considered a relatively safe medication in patients with fractures.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomechanical Phenomena; Diclofenac; Fibula; Fracture Healing; Fractures, Bone; Inflammation; Ketoprofen; Kidney; Liver; Male; Meloxicam; Oxidative Stress; Pain; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles; Tromethamine

Buprenorphine and carprofen, 2 of the most commonly used analgesics in mice, must be administered every 8 to 12 h to provide sustained analgesia. Sustained-release (SR) formulations of analgesics maintain plasma levels that should be sufficient to provide sustained analgesia yet require less frequent dosing and thus less handling of and stress to the animals. The pharmacokinetics of SR formulations of buprenorphine (Bup-SR), butorphanol (Butp-SR), fentanyl (Fent-SR), carprofen (Carp-SR), and meloxicam (Melox-SR) were evaluated in mice over 72 h and compared with those of traditional, nonSR formulations. Bup-SR provided plasma drug levels greater than the therapeutic level for the first 24 to 48 h after administration, but plasma levels of Bup-HCl fell below the therapeutic level by 4 h. Fent-SR maintained plasma levels greater than reported therapeutic levels for 12 h. Therapeutic levels of the remaining drugs are unknown, but Carp-SR provided plasma drug levels similar to those of Carp for the first 24 h after administration, whereas Melox-SR had greater plasma levels than did Melox for the first 8 h. Butp-SR provided detectable plasma drug levels for the first 24 h, with a dramatic decrease over the first 4 h. These results indicate that Bup-SR provides a stable plasma drug level adequate for analgesia for 24 to 48 h after administration, whereas Carp-SR, Melox-SR, Fent-SR, and Butp-SR would require additional doses to provide analgesic plasma levels beyond 24 h in mice.

Topics: Analgesics; Animals; Buprenorphine; Butorphanol; Carbazoles; Delayed-Action Preparations; Female; Meloxicam; Mice; Pain; Thiazines; Thiazoles

Meloxicam is a commonly used COX2-preferential NSAID in both human and veterinary patients. Minimal information has been published regarding appropriate dosing in nonhuman primates. Here we investigated the pharmacokinetic parameters of 3 formulations of meloxicam in cynomolgus macaques. A single dose of meloxicam SR, an extended-release formulation purported to provide therapeutic levels for as long as 72 h, was compared with the intramuscular and oral formulations dosed for 3 consecutive days and as a single dose. The oral formulation, both over 3 d and as a single dose, yielded lower plasma levels and a shorter duration than did intramuscular and sustained-release subcutaneous formulations. The intramuscular formulation, both over 3 d and as a single dose, provided lower plasma levels and a shorter duration than did a sustained-release subcutaneous formulation. The sustained-release formulations generated the highest plasma concentrations for the longest periods of time. None of the formulations caused significant effects on kidney or liver function. Our results indicate that the sustained-release formulation of meloxicam can achieve an adequate steady-state plasma concentration for 2 to 3 d in nonhuman primates. The standard intramuscular formulation provides adequate plasma concentrations for 12 to 24 h, with waxing and waning levels associated with daily dosing. The oral formulation has limited utility in nonhuman primates because of low circulating levels of drug.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Injections, Intramuscular; Macaca fascicularis; Male; Meloxicam; Pain; Thiazines; Thiazoles

The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P<0.05) higher maximum serum concentration (Cmax) when co-administered with meloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (P<0.01) decrease in PGE2 concentration was observed in flunixin-treated animals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; P<0.0001). None of the other drugs significantly affected blood PGE2 levels. Further assessment of oral meloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning.

Topics: Amines; Analgesics; Animals; Area Under Curve; Cattle; Clonixin; Cyclohexanecarboxylic Acids; Dinoprostone; Gabapentin; gamma-Aminobutyric Acid; Half-Life; Horns; Male; Meloxicam; Pain; Random Allocation; Statistics, Nonparametric; Thiazines; Thiazoles

The objectives of this study were to (1) evaluate the use of a pressure algometer and an automated rumination monitoring system to assess changes in pain sensitivity and rumination time in response to endotoxin-induced clinical mastitis and (2) evaluate the effect of the nonsteroidal antiinflammatory drug meloxicam on pain sensitivity and rumination time, as well as other clinical signs, in dairy cattle with endotoxin-induced clinical mastitis. Clinical mastitis was induced in 12 primiparous and 12 multiparous lactating dairy cows by intramammary infusion of 25 µg of Escherichia coli lipopolysaccharide (LPS) into 1 uninfected quarter. Immediately after, half the cows were injected subcutaneously with meloxicam (treated group) and half with the same volume of a placebo solution (control group). Pain sensitivity was assessed by measuring the difference in pressure required to elicit a response on the control and challenged quarter using an algometer 3 d before, immediately before, and at 3, 6, 12, and 24h after LPS infusion and either meloxicam or placebo injection. Rumination was continuously monitored from 2 d before to 3 d after LPS infusion using rumination loggers. Udder edema, body temperature, somatic cell score, and dry matter intake were also monitored to evaluate the occurrence and the duration of the inflammation after LPS infusion. In control animals, the difference in the pressure applied to the control and challenged quarters (control - challenged quarter) increased by 1.1 ± 0.4 kg of force 6h after LPS infusion compared with the baseline, suggesting an increase in pain sensitivity in the challenged quarter. Neither the LPS infusion nor the meloxicam treatment had an effect on daily rumination time. However, the rumination diurnal pattern on the day of LPS infusion showed an overall deviation from the baseline pattern. Cows spent less time ruminating in the hours following LPS infusion and more time ruminating later in the day. Meloxicam did not alter somatic cell score or dry matter intake. However, meloxicam-treated animals had less udder edema and a lower body temperature in the hours following LPS infusion compared with control animals. In conclusion, pressure algometers and rumination loggers show promise as tools to detect mastitis and monitor recovery on farm. Further, meloxicam has a beneficial effect in relieving pain and decreasing udder edema and body temperature in LPS-induced clinical mastitis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Digestion; Female; Lipopolysaccharides; Mastitis, Bovine; Meloxicam; Pain; Pain Management; Pain Measurement; Thiazines; Thiazoles

Adequate pain relief is usually achieved with the simultaneous use of two or more different classes of analgesics, often called multimodal analgesia. The purpose of this article is to highlight the use of perioperative multimodal analgesia and the need to individualize the treatment plan based on the presenting condition, and to adjust it based on the response to analgesia for a given patient. This case series presents the alleviation of acute pain in three cats undergoing different major surgical procedures. These cases involved the administration of different classes of analgesic drugs, including opioids, non-steroidal anti-inflammatory drugs, tramadol, ketamine, gabapentin and local anesthetics. The rationale for the administration of analgesic drugs is discussed herein. Each case presented a particular challenge owing to the different cause, severity, duration and location of pain. Pain management is a challenging, but essential, component of feline practice: multimodal analgesia may minimize stress while controlling acute perioperative pain. Individual response to therapy is a key component of pain relief in cats.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Male; Meloxicam; Pain; Perioperative Period; Thiazines; Thiazoles

Injection anaesthesia with a combination of ketamine and azaperone (K/A) is discussed as a painless alternative to commonly used non-anaesthetized castration. To protect anaesthetized piglets from being crushed, they have to be separated from the sow for 3 h following castration. The aim of this study was to test if this separation and the different treatments would affect short-term behaviour after castration (3 to 6 h after castration) as well as weight gain. Piglets were 5 to 7 days old. Treatment Group 1 received a combination of anaesthesia and analgesia (n = 29, ketamine: 25 mg/kg BW; azaperone: 2 mg/kg BW; meloxicam: 0.4 mg/kg BW), Group 2 received only analgesia (n = 24) and Group 3 received no medication (n = 29). Behaviour and suckling order were compared for a 3 h period the day before castration and after castration. A significantly higher number of teats used by anaesthetized piglets (P = 0.004) suggests a decrease in suckling order stability. There were significant treatment effects between all three groups in the time spent at the sow's teat, with an increase in Group 2 (+69%), decrease in Group 1 (-28%), whereas the control Group 3 (+2%) almost remained unchanged. The anaesthetized piglets showed an increase in the time spent active away from the sow after castration of almost 200% (Groups 2 and 3: ∼50%, P < 0.001). However, no significant treatment effect was seen for weight gain. The results suggest that analgesia has an effect on behaviour, perhaps due to less post-castration pain. This advantage is not apparent for animals receiving additional anaesthesia, probably because of impaired coordination. Although the behavioural changes did not affect weight gain significantly, a decrease in suckling order stability indicates a certain degree of stress due to fighting over teat positions as a consequence of separation. Thus, post-castration behaviour must be taken into account when evaluating alternative castration methods.

Topics: Anesthetics, General; Animal Welfare; Animals; Animals, Newborn; Animals, Suckling; Anti-Inflammatory Agents, Non-Steroidal; Azaperone; Behavior, Animal; Drug Combinations; Injections, Subcutaneous; Ketamine; Male; Meloxicam; Orchiectomy; Pain; Postoperative Period; Sus scrofa; Thiazines; Thiazoles

Immunization with complete Freund adjuvant (CFA) or incomplete Freund adjuvant (IFA) is commonly viewed as painful, yet rodents may not receive analgesics due to concerns that these drugs affect the desired immune responses. Here we tested the hypothesis that pain associated with immunization with CFA or IFA in mice can be relieved without compromising the effectiveness of the immune response. After subcutaneous immunization in the leg with antigen in CFA or IFA, mice were assessed for signs of pain by using behavioral tests, including unrestricted locomotion in an open field, forced running on an automated treadmill, and voluntary wheel running. Effects of the analgesics acetaminophen, meloxicam, and buprenorphine on behavioral and antibody responses were assessed after primary and secondary immunization with the model antigen ovalbumin and after repeated immunization with a limiting dose of recombinant protective antigen from Bacillus anthracis. Open field activity and the distance traveled during forced gait analysis and voluntary wheel running both decreased after immunization. Treatment with each of the analgesics normalized some but not all of these behaviors but did not decrease the mean or maximal antibody titer after primary or repeated immunization with a moderate dose of ovalbumin or after repeated immunization with a limiting dose of protective antigen. In summary, after immunization with CFA or IFA, mice showed behavioral responses suggestive of pain. Acetaminophen, meloxicam, and buprenorphine attenuated these effects without decreasing antibody responses. Therefore, the use of these analgesics for managing rodent pain associated with CFA- or IFA-containing vaccines can be encouraged.

Topics: Acetaminophen; Analgesia; Analgesics; Animals; Animals, Laboratory; Antibody Formation; Behavior, Animal; Buprenorphine; Freund's Adjuvant; Immunization; Lipids; Meloxicam; Mice; Pain; Pain Management; Thiazines; Thiazoles

An 8-yr-old intact female African lion (Panthera leo) presented with a 3-day history of lethargy, anorexia, and vomiting. Hematologic and biochemical abnormalities included a leukocytosis, 41,700/microl (4,700-15,300) with a neutrophilia (37,530/microl; 2,000-9,200) and a left shift (1,250/microl bands; 0-300), and mild hypokalemia of 2.1 mEq/L (2.8-4.8). Abdominal radiographs revealed evidence of intestinal ileus, peritonitis, and the presence of effusion. An exploratory laparotomy was performed, and septic peritonitis due to a pyometra was diagnosed. The lion was treated with an ovariohysterectomy, abdominal lavage, fluid therapy, and a subcutaneous injection of cefovecin. The lion recovered, and clinical signs associated with septic peritonitis resolved within 36 hr. It was returned to conspecifics 3 wk later. Three months postoperatively, the lion showed no residual signs of septic peritonitis.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cephalosporins; Female; Hysterectomy; Lions; Meloxicam; Pain; Peritonitis; Pyometra; Sepsis; Thiazines; Thiazoles

To develop a lameness model to assess the efficacy of analgesics for alleviating pain, swelling and systemic signs of inflammation in sheep.. The response to subcutaneous injection of 0.1 or 0.2 mL turpentine in a forelimb pastern (n = 4 ewes per dose) was examined at 0, 3, 6, 24, 48 and 72 h. In a second experiment, responses were measured at 0, 2, 4, 6, 8, 10, 12 and 24 h in ewes receiving 0.1 mL turpentine ± meloxicam 1 mg/kg IV at 0 h (n = 6 per group). Responses measured included forceplate pressure, skin temperature, limb circumference, nociception, leucocyte count, neutrophil : lymphocyte ratio, haptoglobin and daily feed intake.. Turpentine injection caused a decrease in weight borne on the treated limb, increased skin temperature, increased sensitivity at the injection site and leucocytosis by 2 h and increased limb circumference by 4 h. Weight borne and sensitivity of the injected limb returned to control levels after around 24 h, whereas tissue swelling, elevated skin temperature and elevated haptoglobin levels persisted for at least 72 h. Treatment with meloxicam improved weight borne by and tolerance to pressure exerted on the turpentine-injected limb.. The local and systemic signs of inflammation and pain, temporary reduction in function of the affected limb and partial amelioration of some of these changes by the dose of meloxicam used here suggest that injection of turpentine in the lower forelimb provides a suitable model for examining the efficacy of analgesics for alleviation of pain and inflammation in sheep.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Combinations; Irritants; Lameness, Animal; Meloxicam; Pain; Sheep; Sheep Diseases; Thiazines; Thiazoles; Turpentine

Surgical castration in male piglets is painful and methods that reduce this pain are requested. This study evaluated the effect of local anaesthesia and analgesia on vocal, physiological and behavioural responses during and after castration. A second purpose was to evaluate if herdsmen can effectively administer anaesthesia.. Four male piglets in each of 141 litters in five herds were randomly assigned to one of four treatments: castration without local anaesthesia or analgesia (C, controls), analgesia (M, meloxicam), local anaesthesia (L, lidocaine), or both local anaesthesia and analgesia (LM). Lidocaine (L, LM) was injected at least three minutes before castration and meloxicam (M, LM) was injected after castration. During castration, vocalisation was measured and resistance movements judged. Behaviour observations were carried out on the castration day and the following day. The day after castration, castration wounds were ranked, ear and skin temperature was measured, and blood samples were collected for analysis of acute phase protein Serum Amyloid A concentration (SAA). Piglets were weighed on the castration day and at three weeks of age. Sickness treatments and mortality were recorded until three weeks of age.. Piglets castrated with lidocaine produced calls with lower intensity (p < 0.001) and less resistance movements (p < 0.001) during castration. Piglets that were given meloxicam displayed less pain-related behaviour (huddled up, spasms, rump-scratching, stiffness and prostrated) on both the castration day (p = 0.06, n.s.) and the following day (p = 0.02). Controls had less swollen wounds compared to piglets assigned to treatments M, L and LM (p < 0.001). The proportion of piglets with high SAA concentration (over threshold values 200, 400 mg/l) was higher (p = 0.005; p = 0.05) for C + L compared to M + LM. Ear temperature was higher (p < 0.01) for controls compared to L and LM. There were no significant treatment effects for skin temperature, weight gain, sickness treatments or mortality.. The study concludes that lidocaine reduced pain during castration and that meloxicam reduced pain after castration. The study also concludes that the herdsmen were able to administer local anaesthesia effectively.

Topics: Analgesia; Anesthesia, Local; Anesthetics, Local; Animal Welfare; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Lidocaine; Male; Meloxicam; Orchiectomy; Pain; Random Allocation; Serum Amyloid A Protein; Skin Temperature; Sus scrofa; Sweden; Thiazines; Thiazoles; Vocalization, Animal; Wounds and Injuries

Effects of a single injection of meloxicam on calf behavior, pain sensitivity, and feed and water intakes were examined following dehorning. Sixty Holstein heifer calves were blocked by age and randomly assigned to receive an i.m. injection of meloxicam (0.5 mg/kg) or a placebo. All calves were given a lidocaine cornual nerve block (5 mL per horn). Treatments and nerve blocks were administered 10 min before cautery dehorning. Continuous sampling of behavior was performed during five 1-h intervals using video recordings, and total daily activity was monitored using an accelerometer. A pain sensitivity test was administered with a pressure algometer, and feed and water intakes were recorded daily. Calves were sham-dehorned 24 h before actual dehorning to establish baseline values, and all variables were assessed at the same times following dehorning and sham dehorning for up to 48 h post-dehorning. Meloxicam-treated calves displayed less ear flicking during the 44 h following dehorning (increases of 4.29+/-1.10 and 1.31+/-0.66 ear flicks/h in the first 24 h, and increases of 3.27+/-0.89 and 0.55+/-0.50 ear flicks/h during the second 24 h, for control and meloxicam calves, respectively) and less head shaking during the first 9 h following dehorning (increase of 2.53+/-0.54 and 0.85+/-0.46 headshakes/h over baseline for control and meloxicam, respectively). Meloxicam-treated calves were less active than controls during the first 5 h following dehorning (activity 34.1+/-3.2 and 30.6+/-2.6 for control and meloxicam, respectively) and displayed less sensitivity to pressure algometry 4 h after dehorning (pressure tolerance of 1.62+/-0.13 kg of force and 2.13+/-0.15 kg of force for control and meloxicam calves, respectively). Changes in behavior suggest that meloxicam was effective for reducing post-surgical pain and distress associated with calf dehorning.

Topics: Anesthesia, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Cattle; Dairying; Drinking; Eating; Female; Horns; Meloxicam; Pain; Thiazines; Thiazoles; Video Recording

The aim of the present study was to evaluate and compare the analgesic activity and serum levels of meloxicam (CAS 71125-38-7) after administration of meloxicam associated with beta-cyclodextrin (BCD, CAS 7585-39-9) and unmodified meloxicam. The analgesic activity was measured using the plantar test (rats) and the writhing test (mice). In the plantar test, BCD-meloxicam (3 mg/kg and 10 mg/kg orally) showed higher analgesic activity than corresponding doses of meloxicam alone; in the writhing test BCD-meloxicam (7 mg/kg and 15 mg/kg orally) showed stronger analgesic activity than unmodified meloxicam. Serum levels of meloxicam were significantly higher, at 0.5 h and 1 h after administration of BCD-meloxicam orally than those of unmodified meloxicam (both dosed at 10 mg/kg). The present results suggest that association with beta-cyclodextrin increases the analgesic activity of meloxicam. This may be due to an icreased systemic bioavailability of meloxicam after oral administration of its complex with beta-cyclodextrin.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Carrageenan; Hyperalgesia; Male; Meloxicam; Mice; Pain; Pain Measurement; Rats; Rats, Wistar; Thiazines; Thiazoles; Veins

To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity.. 21 healthy green iguanas (Iguana iguana).. To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg).. There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues.. Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Blood Cells; Body Weight; Female; Iguanas; Injections, Intravenous; Kidney; Male; Meloxicam; Pain; Stomach; Thiazines; Thiazoles

This study examined the effects of a nonsteroidal antiinflammatory agent (NSAID) on physiological responses of calves immediately after hot-iron dehorning (DH) and during the time that local anesthetic (LA) wears off (2 to 3 h) after this procedure. Forty-six calves (33 +/- 0.3 d of age) were randomly assigned to 6 treatments: hot-iron DH versus sham DH with either no pain mitigation, LA alone, or LA with NSAID (i.v. Meloxicam). Eye temperature (measured using infrared thermography) was recorded every 5 min for 3 h after treatments. Heart rate (HR) and heart rate variability (HRV) were recorded continuously; for analysis of HRV, short segments of 512 interbeat intervals were examined. After DH without LA or NSAID, HR increased by 35 +/- 3.0 beats/min in the first 5 min and remained elevated above baseline for 3 h. The HRV around the time of DH did not differ between treatments; however, the root mean square of successive differences decreased from 68 to 41 +/- 12.6 ms immediately following DH without pain relief, suggesting a decrease in vagal tone at this time. Between 2 and 3 h following DH with LA, there was a decrease in eye temperature (-0.6 +/- 0.1 degrees C), an increase in HR (8 +/- 3.0 beats per min) and changes in HRV. Changes in HRV at this time included a decreased high-frequency power and an increase in the low-frequency power and low-frequency/high-frequency ratio, indicating a change in sympatho-vagal balance. The changes in eye temperature, HR, and HRV between 2 and 3 h following DH with LA indicated the onset of pain coinciding with the time that the LA effects wear off. In addition, this study demonstrated that the combination of LA and NSAID mitigated the onset of pain responses when the LA wanes.

Topics: Anesthetics, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Cattle; Dairying; Female; Heart Rate; Horns; Hot Temperature; Lidocaine; Male; Meloxicam; Ocular Physiological Phenomena; Pain; Random Allocation; Thiazines; Thiazoles; Time Factors

Only a few experimental studies have demonstrated the effectiveness of some cyclooxygenase-2 (COX-2) inhibitors for neuropathic pain in diabetic animals. In this study we investigated the usefulness of one such COX-2 inhibitor, meloxicam, for treatment of established diabetic neuropathic pain in mice. Intraperitoneal and perineural injection, but not intrathecal injection, of meloxicam elevated the lowered threshold in the von Frey test. These results suggest that meloxicam exerts antiallodynic effects on established neuropathic pain in diabetic mice, and that the site of its action is peripheral. Meloxicam may therefore be a potentially useful drug for treatment of diabetic neuropathic pain.

Topics: Analgesics; Animals; Cyclooxygenase 2 Inhibitors; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Injections, Intraperitoneal; Injections, Spinal; Male; Meloxicam; Mice; Pain; Pain Measurement; Thiazines; Thiazoles

This study describes the use of a simple questionnaire-based tool to identify behavioural/lifestyle changes that are associated with chronic pain in the cat. These changes were grouped into four behavioural domains (mobility, activity, grooming and temperament). Twenty-three cats with chronic musculoskeletal pain as determined by clinical examination were included. The owners of these cats were asked to complete a questionnaire before and 28 days after the start of analgesic treatment (meloxicam). This included a global assessment of changes in behaviour and assessment of the degree of behavioural change observed within each of the defined domains. The attending veterinary surgeon was independently asked to provide a global score before and after treatment. Both owners and veterinary surgeons reported significant changes in behaviour/lifestyle after analgesic therapy. There was no difference between the owners and veterinary surgeons global assessments at baseline but there was at day 28 (P=0.02). The owners' scores decreased from a median of 5 at baseline to 3 at 28 days (P=0.0004) while the median veterinary surgeon scores decreased from 5 to 2 at 28 days (P<0.0001). There was a statistically significant reduction in the owners' scores for each of the four domains with the greatest reduction occurring in the activity category (P=0.0001). This study shows that owner assessment of changes in their cat's behaviour/lifestyle is an important method of identifying chronic pain in their pets.

Topics: Analgesics; Animals; Behavior, Animal; Cat Diseases; Cats; Chronic Disease; Dogs; Female; Human-Animal Bond; Male; Meloxicam; Musculoskeletal Diseases; Pain; Pain Measurement; Severity of Illness Index; Thiazines; Thiazoles; Time Factors; Treatment Outcome

To determine the effectiveness of two long-acting non-steroidal anti-inflammatory drugs (NSAIDs) at reducing the pain and stress responses to mulesing in lambs.. Merino lambs (n = 60) were allocated at 5 weeks of age to six treatment groups: (1) sham mules; (2) mules; (3) tolfenamic acid-sham mules; (4) tolfenamic acid administered 45 min before mulesing; (5) tolfenamic acid at the time of mulesing; (6) meloxicam at the time of mulesing. Plasma cortisol was measured at -0.75, -0.25, 0, 0.5, 1, 3, 6, 12, 24, 48 and 72 h relative to mulesing. Beta-endorphin concentrations in plasma were determined at 0, 0.5, 1, 6, 12, 24, and 48 h. Haematology was performed on blood samples taken at -0.75, 0, 24, 48 and 72 h. Plasma haptoglobin was measured at 0, 12, 24, 48 and 72 h. Rate of wound healing was determined 72 h post mulesing, and animal behaviour, including posture, was measured for 6 h after mulesing.. The mulesed lambs exhibited large increases in plasma concentrations of cortisol, beta-endorphin and haptoglobin. All mulesed animals lost weight significantly in the week after mulesing, regardless of analgesic administration, but the difference in weight between mulesed and unmulesed lambs was less at the final measurement, 2 weeks after mulesing. Mulesed lambs spent significantly less time lying ventrally than control lambs. All lambs that were mulesed, including those administered NSAIDs, spent more time standing with a hunched posture and less time walking normally than control lambs.. The NSAID treatments applied 45 min before or at the time of mulesing at the dose levels used in this study were not effective in reducing the acute response of lambs to mulesing.

Topics: Analgesics; Animal Welfare; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; beta-Endorphin; Female; Haptoglobins; Hydrocortisone; Male; Meloxicam; ortho-Aminobenzoates; Pain; Posture; Random Allocation; Sheep; Sheep Diseases; Thiazines; Thiazoles; Time Factors; Treatment Outcome; Wound Healing

Sodium urate (SU) synovitis was evaluated as a model for feline arthritic pain using a placebo- and positive-controlled (meloxicam) randomized blinded controlled single crossover design. Monosodium urate crystals [20 mg (1 mL) rod-shaped] were injected into alternate stifles of trained anesthetized cats (n = 3) with a 28 day washout. During the first trial phase, two cats received meloxicam (0.1 mg/kg, PO), a nonsteroidal anti-inflammatory drug (NSAID), for three days before and on the day of SU injection; the third cat received placebo. Treatments and stifles were switched for the second trial. Total force, contact pressure and area of the fore and hind limbs were measured using a pressure mat one day and 0.5 h before, and 2, 4, 6, 8, 10, 24, and 30 h post-SU injection. Skin temperature, joint circumference, analgesia, lameness, and visual analogue scale (VAS) pain scores, were measured at the same times. Comparisons were made for each time and for areas under the curve (AUC) using original and change from baseline; P < 0.05 was significant. Significant differences in force mat data and subjective data were found for the hind limb data (total force and total contact pressure at 6, 10, and 30 h; analgesia and VAS for pain at 4 h; lameness at 10, 24, and 30 h) and for AUC(0)-->(24h) and AUC(0)-->(30 h) (total force, total contact pressure, and mean lameness score) and for differences from BL AUC(0)-->(10h) (total contact area) and AUC(0)-->(24h) (total contact area and mean lameness score) and AUC(0)-->(30 h) (total force, total contact area, and mean lameness). No cats required rescue analgesia. Injection of 1 mL of monosodium urate into the stifle of a cat causes moderate transitory pain and was suitable for assessing analgesic efficacy of an NSAID with a pressure mat and subjective criteria.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Area Under Curve; Cats; Female; Inflammation; Lameness, Animal; Meloxicam; Osteoarthritis; Pain; Pain Measurement; Pilot Projects; Severity of Illness Index; Synovitis; Thiazines; Thiazoles; Uric Acid

The objective of this study was to examine the nature of interaction between cyclooxygenase-2 inhibitor meloxicam and inducible nitric oxide synthase inhibitor aminoguanidine in formalin-induced nociception in mice and the possible therapeutic advantage.. Antinociceptive effect of meloxicam (1, 3, 10 and 30 mg/kg, oral) and aminoguanidine (10, 30, 100 and 300 mg/kg, oral) and their combinations was examined in formalin-induced paw licking model in mice. Analysis of variance and isobolographic method were employed to identify the nature of antinociceptive interaction.. Higher doses of meloxicam (10 and 30 mg/kg) and aminoguanidine (100 and 300 mg/kg) produced significant reduction in paw licking time (antinociceptive) in late phase of formalin-induced nociception. Combination of sub-threshold dose of meloxicam (3 mg/kg) with increasing doses of aminoguanidine (10, 30, 100 and 300 mg/kg) resulted in synergistic antinociceptive effect. Similarly, co-administration of sub-threshold dose of aminoguanidine (30 mg/kg) with increasing doses of meloxicam (1, 3, 10 and 30 mg/kg) produced significant reduction in formalin-induced paw licking behaviour. The experimental ED(50) for combination with their confidence limits are below the confidence interval of theoretical line of additive interaction, suggesting synergistic nature of interaction between meloxicam and aminoguanidine in isobolographic analysis.. Co-administration of meloxicam and aminoguanidine showed synergistic antinociceptive effect which might possibly reduce gastrointestinal toxicity associated with the use of meloxicam.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Formaldehyde; Guanidines; Male; Meloxicam; Mice; Nitric Oxide Synthase Type II; Nociceptors; Pain; Pain Measurement; Thiazines; Thiazoles

An adult male white Bengal tiger (Panthera tigris tigris) with pronounced atrophy of the pelvic musculature was diagnosed with degenerative osteoarthritis of the coxofemoral joints. Initial management with the nonsteroidal anti-inflammatory drug meloxicam and a semisynthetic sodium pentosan polysulfate resulted in clinical improvement and radiographic stabilization of the arthritic condition over several months. However, because pain was still evident, bilateral denervation of the coxofemoral joints was performed, successfully ameliorating the signs of osteoarthritic pain in the tiger. Meloxicam has shown good clinical efficacy for the treatment of osteoarthritis and other painful conditions in large felids. Coxofemoral joint denervation offers many advantages for the treatment of osteoarthritis in exotic carnivore species, and should be considered a viable treatment modality.

Topics: Animals; Animals, Wild; Anti-Inflammatory Agents, Non-Steroidal; Combined Modality Therapy; Denervation; Hip Joint; Male; Meloxicam; Osteoarthritis; Pain; Thiazines; Thiazoles; Tigers; Treatment Outcome

The possible participation of K+ channels in the antinociceptive action of meloxicam was assessed in the 1% formalin test. Local peripheral administration of meloxicam produced a dose-dependent antinociception only during the second phase of the formalin test. K+ channel blockers alone did not modify formalin-induced nociceptive behavior. However, local peripheral pretreatment of the paw with charybdotoxin and apamin (large- and small-conductance Ca2+-activated K+ channel inhibitors, respectively), 4-aminopyridine and tetraethylammonium (non-selective voltage-dependent K+ channel inhibitors), but not glibenclamide or tolbutamide (ATP-sensitive K+ channel inhibitors), dose-dependently prevented meloxicam-induced antinociception. It is concluded that meloxicam could open large- and small-conductance Ca2+-activated K+ channels, but not ATP-sensitive K+ channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K+ channels was also suggested, but since non-selective inhibitors were used the data await further confirmation.

Topics: 4-Aminopyridine; Analgesics, Non-Narcotic; Analysis of Variance; Animals; Apamin; Behavior, Animal; Charybdotoxin; Dose-Response Relationship, Drug; Female; Formaldehyde; Glyburide; Meloxicam; Pain; Pain Measurement; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Potassium Channels, Inwardly Rectifying; Rats; Rats, Wistar; Tetraethylammonium; Thiazines; Thiazoles; Tolbutamide

Lines of evidence have indicated that cyclooxygenase 2 plays a role in the pathophysiology of neuropathic pain. However, the site and mechanism of its action are still unclear. Spinal glia has also been reported to mediate pathologic pain states. The authors evaluated the effect of continuous intrathecal or systemic cyclooxygenase-2 inhibitor on the development and maintenance of neuropathic pain and glial activation in a spinal nerve ligation model of rats.. Continuous intrathecal infusion of meloxicam (32 or 320 mug . kg . day) or saline was started immediately after L5-L6 spinal nerve ligation. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively. Spinal astrocytic activation was evaluated with glial fibrially acidic protein immunoreactivity on day 7. In other groups of rats, continuous intrathecal meloxicam was started 7 days after spinal nerve ligation, and effects on established neuropathic pain and glial activation were evaluated. Last, effects of continuous systemic meloxicam (16 mg . kg . day) on existing neuropathic pain and glial activation were examined.. Intrathecal meloxicam prevented the development of mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation. It also inhibited spinal glial activation responses. In contrast, when started 7 days after the nerve ligation, intrathecal meloxicam did not reverse established neuropathic pain and glial activation. Systemic meloxicam started 7 days after ligation partially reversed neuropathic behaviors but not glial activation.. Spinal cyclooxygenase 2 mediates the development but not the maintenance of neuropathic pain and glial activation in rats. Peripheral cyclooxygenase 2 plays a part in the maintenance of neuropathic pain.

Topics: Animals; Cyclooxygenase 2; Male; Meloxicam; Neuroglia; Pain; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Spinal Cord; Thiazines; Thiazoles

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Lumbar Vertebrae; Male; Meloxicam; Middle Aged; Osteochondritis; Pain; Severity of Illness Index; Thiazines; Thiazoles

To compare the effectiveness of preoperative PO and SC administration of buprenorphine and meloxicam for prevention of postoperative pain-associated behaviors in cats undergoing ovariohysterectomy.. Randomized controlled study.. 51 female cats (4 to 60 months old; weight range, 1.41 to 4.73 kg [3.1 to 10.4 lb]).. Cats received 1 of 5 treatments at the time of anesthetic induction: buprenorphine PO (0.01 mg/kg [0.0045 mg/lb]; n = 10), buprenorphine SC (0.01 mg/kg; 10), meloxicam SC (0.3 mg/kg 10.14 mg/lb]; 10), meloxicam PO (0.3 mg/kg; 10), or 0.3 mL of sterile saline (0.9% NaCI) solution SC (control group; 11). Sedation scores and visual analog scale and interactive visual analog scale (IVAS) pain-associated behavior scores were assigned to each cat 2 hours before and at intervals until 20 hours after surgery.. Cats receiving meloxicam PO or SC had significantly lower IVAS scores (2.91 and 2.02, respectively), compared with IVAS scores for cats receiving buprenorphine PO (755). Pain-associated behavior scores for cats administered buprenorphine or meloxicam PO or SC preoperatively did not differ significantly from control group scores. Rescue analgesia was not required by any of the cats receiving meloxicam, whereas 3 of 10 cats receiving buprenorphine PO, 2 of 10 cats receiving buprenorphine SC, and 1 of 11 cats receiving the control treatment required rescue analgesia.. On the basis of pain-associated behavior scores, cats receiving meloxicam PO or SC before ovariohysterectomy appeared to have less pain after surgery than those receiving buprenorphine PO preoperatively.

Topics: Administration, Oral; Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Behavior, Animal; Buprenorphine; Cats; Drug Administration Routes; Female; Hysterotomy; Injections, Subcutaneous; Meloxicam; Ovariectomy; Pain; Postoperative Care; Thiazines; Thiazoles; Time Factors; Treatment Outcome

Very little is known concerning the occurrence of pain in cancer research models. We wished to establish whether a behaviour-based approach, originally developed to assess postoperative pain, could be used to determine positive effects of the analgesics carprofen and meloxicam in rats that might be experiencing pain during tumour development in an orthotopic model of bladder cancer. An invasive but non-metastatic rat bladder cancer cell line was surgically implanted into the bladder wall of 57 inbred Fisher344 rats. The rats underwent daily clinical assessments. When clinical signs consistent with chronic pain were apparent, behavioural data were collected from 44 animals during 2 x 10 min periods, immediately before and one hour after a subcutaneous injection of either physiological saline (0.9%; 0.2 ml/100 g), carprofen (5 mg/kg) or meloxicam (2 mg/kg). Treatment-associated behaviour changes were then compared between groups. The lack of active behaviour, both before and after each treatment, was consistent with established clinical signs of pain. The rats were so inactive following the treatment that the behavioural technique we had previously developed was of comparatively little use in determining either pain severity or analgesic efficacy. One very prominent effect, however, was an increase in ventral abdominal licking in the control (saline) group. As this was absent in rats given meloxicam or carprofen, and has previously been considered to indicate pain emanating from damaged tissue, it was concluded that the analgesic-treated rats gained at least some benefit from the drug treatments, but it was not possible to gauge the extent of this. Handling for examination or treatment may have intensified pain in rats in the control group, and so this should be avoided whenever possible. It is likely that post-surgical pain differs markedly from cancer pain, so a different set of behavioural markers may be needed to assess it effectively. More intensive behaviour monitoring may help to develop a suitable technique for detecting the onset of, and assess the severity of pain that may occur during tumour development.

Topics: Analysis of Variance; Animals; Behavior, Animal; Carbazoles; Disease Models, Animal; Male; Meloxicam; Pain; Pain Measurement; Pain, Postoperative; Rats; Rats, Inbred F344; Thiazines; Thiazoles; Urinary Bladder Neoplasms

The effects of a synthetic peptide analog of thymulin (PAT) were tested on nociceptive behavior in two animal models for peripheral mononeuropathy and in another two models for capsaicin-induced hyperalgesia. Treatment with PAT (0.25-25 microg/rat, i.p.) produced significant reduction of the mechanical allodynia and heat hyperalgesia in rats subjected to either chronic constriction injury (CCI) or spared nerve injury (SNI) models for mononeuropathy. Cold allodynia was moderately reduced in the CCI model. The inhibition of neuropathic manifestations peaked at 1-2 h post-treatment and disappeared in 3-4 h. Daily treatment with PAT, however, produced progressive attenuation of all neuropathic manifestations in the SNI model. On the other hand, pretreatment with similar doses of PAT produced dose-dependent reduction of the hyperalgesia induced by intraplantar injection of capsaicin (10 microg in 50 microl). The highest dose of PAT (50 microg) produced significant reduction of abdominal aversive behavior induced by i.p injection of capsaicin (20 microg in 100 microl). Compared with the effects of treatment with morphine or meloxicam (injected at single doses known to produce analgesia), PAT exerted equal or stronger inhibitory effects on neuropathic manifestations. The reported results suggest a possible direct action of PAT on afferent nerve fibers but its mechanisms remain to be determined.

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Animals; Capsaicin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Hot Temperature; Hyperalgesia; Ligation; Male; Meloxicam; Morphine; Pain; Pain Threshold; Peptides; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Reaction Time; Thiazines; Thiazoles; Thymic Factor, Circulating; Time Factors

To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy.. 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses.. Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration.. Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups.. Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Butorphanol; Carbazoles; Dog Diseases; Dogs; Female; Male; Meloxicam; Narcotic Antagonists; Pain; Synovitis; Thiazines; Thiazoles

Tizanidine, an alpha2-adrenergic receptor agonist with myospasmolytic action, is indicated for the treatment of back pain either as monotherapy or in combination with nonsteridal anti-inflammatory drugs (NSAIDs). Tizanidine (0.25-1.0 mg/kg) significantly produced analgesic and anti-inflammatory effect in acetic acid induced writhing in mice and carrageenan-induced paw edema in rats, respectively. The effects were comparable with clonidine (0.25 and 0.50 mg/kg), another alpha2-agonist. Yohimbine (1 mg/kg), alpha2-adrenergic antagonist reversed the effect of tizanidine. Tizanidine (0.25 mg/kg) and clonidine (0.25 mg/kg) significantly potentiated the antinociceptive and anti-inflammatory effect of NSAIDs (nimesulide, meloxicam and naproxen). Tizanidine (1 mg/kg) did not alter basal pH, acidity (free and total) of gastric content and did not produce any mucosal injury in fasted rats. Tizanidine (1 mg/kg) significantly reduced meloxicam (UD50 3.21 mg/kg), nimesulide (UD50 24.52 mg/kg) and naproxen (UD50 14.10 mg/kg)-induced ulcerogenic effect (ulcer index, pH and free/total acidity). It is expected that tizanidine exerted gastrotprotection through stimulation of gastric and central alpha2-adrenergic receptors. Present investigation suggested that tizanidine not only enhance the analgesic and anti-inflammatory effect of NSAIDs but also improved gatstrointestinal tolerability of NSAIDs through modulation of central alpha-2-receptors. From this study, it can be speculated that tizanidine and NSAID combination therapy would prove to be a novel approach to treat nociceptive/inflammatory conditions with improved gastric tolerability of NSAIDs.

Topics: Adrenergic alpha-Agonists; Animals; Anti-Inflammatory Agents, Non-Steroidal; Clonidine; Drug Synergism; Drug Therapy, Combination; Meloxicam; Mice; Naproxen; Pain; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-2; Stomach Ulcer; Sulfonamides; Thiazines; Thiazoles; Yohimbine

A 6-month-old bullmastiff was presented with bilateral painful swellings of the mandible. Craniomandibular osteopathy was diagnosed based on skull radiographs and histological findings from bone biopsies. Treatment consisted of meloxicam to alleviate the pain. Three months later, the dog was pain free without medication or palpable change in the mandible.

Topics: Analgesics, Non-Narcotic; Animals; Bone Diseases, Developmental; Craniomandibular Disorders; Dog Diseases; Dogs; Female; Mandible; Meloxicam; Pain; Radiography; Thiazines; Thiazoles

1. The common mechanism of action of non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of the enzyme cyclo-oxygenase (COX), however, this inhibition is not enough to completely account for the efficacy of these agents in several models of acute pain. 2. It has been demonstrated that cholinergic agents can induce antinociception, but the nature of the interaction between these agents and NSAIDs drugs has not been studied. The present work evaluates, by isobolographic analysis, the interactions between the cholinergic indirect agonist neostigmine (NEO) and NSAIDs drugs, using a chemical algesiometric test. 3. Intraperitoneal (i.p.) or intrathecal (i.t.) administration of NEO and of the different NSAIDs produced dose-dependent antinociception in the acetic acid writhing test of the mouse. 4. The i.p. or i.t. co-administration of fixed ratios of ED(50) fractions of NSAIDs and NEO, resulted to be synergistic or supra-additive for the combinations ketoprofen (KETO) and NEO, paracetamol (PARA) and NEO) and diclofenac (DICLO) and NEO administered i.p. However, the same combinations administered i.t. were only additive. In addition, the combinations meloxicam (MELO) and NEO and piroxicam (PIRO) and NEO, administered either i.p. or i.t., were additive. 5. The results suggest that the co-administration of NEO with some NSAIDs (e.g. KETO, PARA or DICLO) resulted in a synergistic interaction, which may provide evidence of supraspinal antinociception modulation by the increased acetylcholine concentration in the synaptic cleft of cholinergic interneurons. The interaction obtained between neostigmine and the NSAIDs could carry important clinical implications.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholinesterase Inhibitors; Diclofenac; Disease Models, Animal; Drug Synergism; Ketoprofen; Meloxicam; Mice; Neostigmine; Pain; Pain Measurement; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles

This study examined the effects of the cyclooxygenase-2 (COX-2) inhibitor, meloxicam, on responses of spinal dorsal horn neurones to synaptic inputs in vivo. Experiments were run using male Sprague-Dawley rats (350-375 g) anesthetized with Na-pentobarbital (50 mg/kg, i.p.) and acutely spinalized at T9. Spinal segments L1-4 were exposed for extracellular single unit recording of on-going and stimulation-evoked activity of eight wide dynamic range neurones. On-going activity was unaffected by meloxicam (0.1 mg/kg, i.v.). However, responses to noxious mechanical stimulation (21 N for 3 s) of the cutaneous receptive field of the hind paw were depressed by meloxicam in particular the afterdischarge (34.50 +/- 6.06% inhibition) in all eight neurones studied. The brief initial discharge in response to stimulation was depressed less (15.31 +/- 4.89% inhibition, n = 7/8). The data indicate that the percent inhibition of the afterdischarge was significantly greater than that of the initial discharge (P < 0.05). Given the selectivity of meloxicam for COX-2, the data suggest that COX-2 may be involved in mediating and/or modulating excitatory effects of nociceptive inputs to dorsal horn neurones, in particular the prolonged stimulation-evoked afterdischarge.

Topics: Analgesics, Non-Narcotic; Animals; Male; Meloxicam; Neurons; Pain; Physical Stimulation; Rats; Rats, Sprague-Dawley; Spinal Cord; Thiazines; Thiazoles

1. Although sodium channel blockers are effective analgesics in neuropathic pain, their effectiveness in inflammatory pain has been little studied. Sodium channels are substantially up-regulated in inflamed tissue, which suggests they play a role in maintenance of chronic inflammatory pain. We have examined the effects of sodium channel blockers on mobility, joint hyperalgesia and inflammation induced by complete Freund's adjuvant injected in one ankle joint of adult rats. The clinically effective sodium channel blocker, mexiletine, was compared with crobenetine (BIII 890 CL), a new, highly use-dependent sodium channel blocker. 2. Rats were treated for 5 days, starting on the day of induction of arthritis and were tested daily for joint hyperalgesia, hind limb posture and mobility. At post-mortem, joint stiffness and oedema were assessed. Dose response curves were constructed for each test compound (3 - 30 mg kg day(-1)). Control groups were treated with vehicle or with the non-steroidal anti-inflammatory drug, meloxicam (4 mg kg day(-1) i.p.). 3. Both sodium channel blockers produced dose dependent and significant reversal of mechanical joint hyperalgesia and impaired mobility with an ID50 of 15.5+/-1.1 mg kg day(-1) for crobenetine and 18.1+/-1.2 mg kg day(-1) for mexiletine. Neither compound affected the responses of the contralateral non-inflamed joint, nor had any effect on swelling and stiffness of the inflamed joint. 4. We conclude that sodium channel blockers are analgesic and anti-hyperalgesic in this model of arthritis. These data suggest that up regulation of sodium channel expression in primary afferent neurones may play an important role in the pain and hyperalgesia induced by joint inflammation.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Benzomorphans; Dose-Response Relationship, Drug; Female; Freund's Adjuvant; Hyperalgesia; Inflammation; Meloxicam; Mexiletine; Pain; Pain Measurement; Posture; Rats; Rats, Wistar; Sodium Channel Blockers; Thiazines; Thiazoles

The involvement of the nitric oxide-cyclic GMP pathway in the antinociceptive action of the cyclooxygenase-2 preferential inhibitor meloxicam was assessed in the rat formalin test. Rats received local pretreatment with saline or meloxicam and then 50 microl of dilute formalin (1%). Local administration of meloxicam produced a dose-dependent antinociception in the second phase of the formalin test. The antinociception produced by meloxicam was due to a local action as its administration in the contralateral paw was ineffective. Local pretreatment of the paws with saline or N(G)-D-nitro-arginine methyl ester (D-NAME) did not affect the antinociception produced by meloxicam. However, N(G)-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor) or 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor) blocked in a dose-dependent way the effect of meloxicam. It is concluded that the peripheral antinociceptive effect of meloxicam involves a local NO-cyclic GMP pathway.

Topics: Analgesics, Non-Narcotic; Animals; Cyclic GMP; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Formaldehyde; Guanylate Cyclase; Meloxicam; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxadiazoles; Pain; Pain Measurement; Quinoxalines; Rats; Rats, Wistar; Thiazines; Thiazoles

We have recently reported that intraperitoneal (i.p.) injection of thymulin at low doses (50 ng) resulted in thermal and mechanical hyperalgesia and upregulation of the level of interleukin-1beta in the liver. In this study, we demonstrate that such injections of thymulin result in a significant elevation in the levels of TNF-alpha (P<0.01), NGF (P<0.01) and PGE(2) (P<0.01) in the liver of the treated rats, in addition to the increase in the levels of IL-1beta. Pretreatment with specific antagonists to each of these factors (polyclonal anti-TNF-alpha, anti-NGF antiserum and IL-1 receptor antagonist) did not result in the abolition of the hyperalgesia as assessed by the paw pressure, hot plate, paw immersion and tail flick tests. However, pretreatment with a combination of the above antagonist and antisera almost completely prevented thymulin-induced hyperalgesia. The cyclooxygenase inhibitor, meloxicam, reversed in a dose dependent manner (0.2, 0.4 and 2 mg/kg) thymulin effects as assessed by the different pain tests. It also abolished the thymulin-induced increase in the level of cytokines and NGF in the liver. Our results indicate that PGE(2) could be the key mediator of the hyperalgesic action of thymulin and the observed upregulation of proinflammatory cytokines and NGF.

Topics: Analgesics, Non-Narcotic; Animals; Cytokines; Dinoprostone; Dose-Response Relationship, Drug; Hyperalgesia; Immune Sera; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Male; Meloxicam; Nerve Growth Factor; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Sialoglycoproteins; Thiazines; Thiazoles; Thymic Factor, Circulating; Time Factors; Tumor Necrosis Factor-alpha

Non-steroidal anti-inflammatory drugs inhibit constitutive (COX-1) and induced cyclooxygenase (COX-2), blocking prostaglandin production. We have compared the effects on nociceptive reflexes of meloxicam, which is COX-2 selective, with indomethacin, which is non-selective, using an in vitro spinal cord preparation. Cords were taken from naive rats, and from rats with carrageenan-induced hyperalgesia of one hindpaw. Reflex thresholds were lower in carrageenan preparations. Superfusion with meloxicam (10-100 microM) dose-dependently inhibited baseline reflexes and wind-up in normal and carrageenan preparations, whereas indomethacin (100-300 microM) had no effect. Thus meloxicam inhibits spinal reflexes, whereas indomethacin does not, despite its high affinity for both COX isoforms. We conclude that meloxicam has spinal antinociceptive actions which cannot be explained by the current concept of COX inhibition.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Electric Stimulation; Female; Hindlimb; Hyperalgesia; In Vitro Techniques; Indomethacin; Isoenzymes; Male; Meloxicam; Membrane Proteins; Pain; Perfusion; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Spinal Cord; Spinal Nerve Roots; Thiazines; Thiazoles

The antinociceptive effect of the new cyclooxygenase (COX)-2 inhibitor, meloxicam, given intraperitoneally (i.p.), was assessed in different models of chemical and thermal nociception in mice.. The analgesic effect was analysed using acetic acid-induced abdominal constriction (AA), formalin and capsaicin-induced licking, and hot-plate tests.. The treatment of animals with meloxicam or diclofenac (2.8-94.3 micromol/kg, i.p. 30 min prior) caused graded and significant inhibition of AA, with mean ID50 values of 7.4 and 38.0 micromol/kg, respectively. At the ID50 level, meloxicam was about 5-fold more potent than diclofenac. In the formalin test, meloxicam or diclofenac (0.8-94.3 micromol/kg, i.p. 30 min prior) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking. The calculated mean ID50 values for the early phase were: 7.1 and > 94.3 micromol/kg, while for the late phase they were 2.8 and 34.5 micromol/kg, respectively, for meloxicam and diclofenac. Meloxicam also caused significant inhibition of formalin-induced oedema (p < 0.05). Meloxicam and diclofenac (0.8-314.4 micromol/kg, i.p. 30min prior) produced significant and dose-related inhibition of neurogenic nociception caused by topical injection of capsaicin, with mean ID50 values of 4.0 and 47.4 micromol/kg, respectively, but were ineffective in the hot-plate model of nociception.. The present study shows that meloxicam dose-dependently exhibited systemic antinociceptive action when assessed against neurogenic and inflammatory pain caused by acetic acid, formalin and capsaicin models. In contrast, when assessed in the hot-plate test, meloxicam had no significant effect. Thus, meloxicam and other COX-2 inhibitors might be useful for therapeutic intervention in the management of neurogenic and inflammatory pain.

Topics: Abdominal Muscles; Acetic Acid; Analgesics; Analgesics, Opioid; Animals; Capsaicin; Cyclooxygenase Inhibitors; Diclofenac; Formaldehyde; Inflammation; Male; Meloxicam; Mice; Morphine; Muscle Contraction; Pain; Pain Measurement; Reaction Time; Thiazines; Thiazoles

The anti-inflammatory, analgesic and antipyretic properties of the new non-steroidal anti-inflammatory agent, meloxicam, were investigated in a variety of animal models and compared with the properties of piroxicam, diclofenac, indomethacin and several other NSAIDs. With respect to the total effect of a single oral dose, the anti-exudative effect of meloxicam on carrageenan-induced oedema in the rat exceeded that of all the NSAIDs included in the comparison. Additionally, meloxicam showed the greatest potency of all the compounds examined with respect to adjuvant-induced arthritis in the rat, the granuloma pouch model and the cotton pellet test in the rat. Unlike indomethacin, in the carrageenan pleurisy model in the rat, meloxicam caused both a dose-dependent reduction in exudate volume and also inhibition of leucocyte migration. Meloxicam showed a strong and lasting effect on inflammatory pain in the rat. Like other NSAIDs, but unlike dipyrone, meloxicam had no effect in the hot plate and tail clamp tests, which are used to identify weak central analgesic effects. Unlike dipyrone and like indomethacin, meloxicam had no effect in a model of visceral distention pain. In common with other NSAIDs, meloxicam had no influence on the body temperature of normothermic rats in the anti-inflammatory dose range, but did reduce yeast-induced fever in the rat in a dose-dependent manner. Like piroxicam, meloxicam had a uricosuric effect on rats treated with oxonic acid. Low-dose meloxicam inhibited both bradykinin-induced and PAF-induced bronchospasm in the guinea-pig, but had no effect on acetylcholine-induced bronchospasm. Piroxicam had greater ulcerogenic effects in the rat stomach than meloxicam. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of piroxicam, indomethacin, diclofenac and naproxen.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bronchial Spasm; Chemotaxis, Leukocyte; Fever; Guinea Pigs; In Vitro Techniques; Inflammation; Male; Meloxicam; Mice; Pain; Pain Measurement; Rats; Stomach Ulcer; Thiazines; Thiazoles; Uricosuric Agents