lornoxicam and Pain

Lornoxicam (chlortenoxicam), a new nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties, is available in oral and parenteral formulations. It is distinguished from established oxicams by a relatively short elimination half-life (3 to 5 hours), which may be advantageous from a tolerability standpoint. Data from preliminary clinical trials suggest that lornoxicam is as effective as the opioid analgesics morphine, pethidine (meperidine) and tramadol in relieving postoperative pain following gynaecological or orthopaedic surgery, and as effective as other NSAIDs after oral surgery. Lornoxicam was also as effective as other NSAIDs in relieving symptoms of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute sciatica and low back pain. Lornoxicam has a tolerability profile characteristic of an NSAID, with gastrointestinal disturbances being the most common adverse events. Limited clinical experience to date suggests that, as with a number of other NSAIDs, lornoxicam may provide a better-tolerated alternative or adjuvant to opioid analgesics for the management of moderate to severe pain. It has also demonstrated potential as an alternative to other NSAIDs for the management of arthritis and other painful and inflammatory conditions. These preliminary findings require confirmation in further comparative and long term studies.

Topics: Absorption; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dosage Forms; Drug Interactions; Humans; Low Back Pain; Migraine Disorders; Osteoarthritis; Pain; Pain, Postoperative; Piroxicam; Spondylitis, Ankylosing; Tissue Distribution

In dental applications, as in all other medical applications, pain needs to be prevented or at least controlled. The use of the tooth as a model for studying pain mechanisms is well established. In the current study, we aimed to evaluate and compare the analgesic effects of gabapentin and lornoxicam, respectively, vs a placebo for postendodontic treatment pain.. Clinical research was planned as prospective, randomized, and placebo controlled. Each subject was given 600 mg gabapentin (group G: N = 30), 8 mg lornoxicam (group L: N = 30), or a placebo (group C: N = 30) 30 min prior to endodontic treatment.. At 4 (T(3)), 8 (T(4)), 12 (T(5)), and 24 (T(6)) h after preoperative (T(0)) time points, the analgesic efficacies of the agents were evaluated by using the visual analog scale (VAS).. In group G, VAS values were significantly greater at T(0) time point than at T(5) or T(6). T(0) time point VAS value in group L was lower than at T4 time point and greater than at T(6). In group C, T(0) time point VAS values were significantly lower at T(3) and T(5) time points and greater than at T(6) time point. VAS values in group G at T(5) time point were significantly lower than in group C or group L (P < 0.05).. Based on the obtained data, prophylactic lornoxicam controlled postendodontic treatment pain more effectively than did the placebo drugs, and gabapentin was more effective in controlling the pain than either lornoxicam or the placebo.

Topics: Adult; Amines; Analgesics; Cyclohexanecarboxylic Acids; Double-Blind Method; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Pain; Pain Management; Pain Measurement; Piroxicam; Prospective Studies; Root Canal Therapy

Extracorporeal shockwave lithotripsy (SWL) is the mainstay treatment modality for upper urinary tract stones. However, it is a relatively painful procedure and so an efficient analgesia is required for better clinical success. The ideal method of anesthesia has not been standardized. The objective of this randomized study, for the first time in the literature, was to compare the efficacy of three common analgesics, each belonging to a different group, in pain control during SWL.. In this randomized controlled study, 90 patients with upper urinary tract stones undergoing SWL were randomly divided into three groups. Group I (n = 30) received 1 g of paracetamol, group II (n = 30) received 8 mg of lornoxicam, and group III (n = 30) had 1 mg/kg of tramadol. No premedication was applied in all groups. Pain scores by visual analog scale (VAS), blood pressure, heart rate, respiratory rate, and peripheral oxygen saturation were noted before procedure and at 1 minute and every 5 minutes during the SWL. Supplementary analgesic consumption was recorded. Moreover, all adverse effects and both patient and urologist satisfaction were documented.. Demographic parameters of the three groups were similar. All monitored parameters were also not different among the groups. The mean VAS scores at all measured times during SWL were below 4 except for two occasions, indicating a relatively efficient overall pain control provided by these three medications. Moreover, the mean VAS scores were similar among these three groups at all measured times during SWL except for those at 5 and 20 minutes at which groups III and II showed lesser pain control, respectively. No difference was observed in the amount of supplementary analgesia, which was required at higher voltages in a majority of patients. There was no significant difference in side effects.. This study suggests that paracetamol, lornoxicam, and tramadol can be safely and efficiently preferred in pain control during SWL.

Topics: Acetaminophen; Adult; Analgesics; Demography; Female; Humans; Lithotripsy; Male; Middle Aged; Pain; Pain Measurement; Piroxicam; Tramadol; Treatment Outcome; Young Adult

Parenteral non-steroidal anti-inflammatory drugs (NSAIDs) are useful agents in the treatment of postoperative pain and other acute traumatic painful conditions such as fractures. Clinical trials with lornoxicam, an oxicam derivative, document its efficacy as a potent analgesic with excellent anti-inflammatory properties in painful and or/inflammatory conditions including postoperative pain and arthritic conditions. However, there is no documentation of the efficacy and tolerability of intravenous lornoxicam in Indian patients with acute painful conditions such painful traumatic conditions requiring hospitalisation and parenteral analgesics. The present study was undertaken to evaluate the efficacy and tolerability of intravenous lornoxicam in Indian patients with postoperative pain or other acute painful traumatic conditions requiring hospitalisation and parenteral analgesia in in-office practice conditions. In this multicentric, prospective, open, non-comparative phase IV, postmarketing surveillance study patients admitted in the nursing home for either postoperative pain or painful conditions requiring hospitalisation and parenteral analgesia were enrolled in the study after obtaining their informed consent. Of the 161 patients fulfilling the selection criteria, 148 met the selection criteria and were included in the efficacy analysis. Patients were treated with intravenous lornoxicam 8 mg twice or three times daily as required for up to 3 days. Efficacy variables included changes in severity of pain scores compared to baseline values, onset of pain relief and overall global efficacy. Tolerability was assessed through monitoring of treatment-emergent adverse events, physical examination, assessments of vital signs, and overall global assessment of tolerability. Results indicated that within 1 hour of administration of intravenous lornoxicam, the mean scores of pain severity were reduced by 39.46% and by 6 hours, there was a further 52% reduction in the mean scores. Therapy with intravenous lornoxicam was associated with a faster onset of action with 15.4% patients reporting pain relief within 10 minutes and 55.9% patients within 10 to 30 minutes. Overall, global assessment of efficacy was rated as good to excellent in 95.3% of the patients. Therapy with intravenous lornoxicam was well tolerated with only 5 patients reporting adverse events such as headache (n=3) and gastritis (n=1) of mild to moderate intensity but transient. Overall, global tolerabilit

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pain; Pain Measurement; Piroxicam; Prospective Studies; Treatment Outcome; Young Adult

Lornoxicam like other non-steroidal anti-inflammatory drugs (NSAIDs) is widely used for postoperative pain therapy. Evaluation of the effect of lornoxicam on cerebral processing of surgical pain was thus the aim of the present functional magnetic resonance imaging (fMRI) study.. An fMRI-compatible pain model that mimics surgical pain was used to induce pain rated 4-5 on a visual analogue scale (VAS) at the anterior margin of the right tibia in volunteers (n=22) after i.v. administration of saline (n=11) or lornoxicam (0.1 mg kg(-1)) (n=11).. Lornoxicam, which significantly reduced pain sensation [VAS: mean (sd) 4.6 (0.7) vs 1.2 (1.5)], completely suppressed pain-induced activation in the SII/operculum, anterior cingulate cortex, insula, parietal (inferior), prefrontal (inferior, medial), temporal (inferior, medial/superior) lobe, cerebellum, and contralateral (e.g. left-sided) postcentral gyrus (SI). Only the hippocampus and the contralateral superior parietal lobe (BA 7) were activated.. As compared with saline, lornoxicam typically suppressed pain-induced brain activation in all regions except the hippocampus. Furthermore, de novo activation was found in the contralateral, superior parietal lobe (BA 7).

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Male; Pain; Pain Measurement; Physical Stimulation; Piroxicam; Single-Blind Method

To evaluate the efficacy of 2 different doses of intravenous lornoxicam for pain relief during shock wave lithotripsy (SWL).. In this randomized, controlled, double-blind study, 60 ASA I-II patients undergoing SWL were randomly divided into 3 groups. Fifteen minutes before SWL, 4 mL of saline solution was given to the patients in group I, 8 mg lornoxicam in group II, and 16 mg lornoxicam in group III. All groups received 1 mcg/kg fentanyl intravenously 3 minutes before SWL. Pain scores, blood pressure, heart rate, respiratory rate, and oxygen saturation were noted before SWL, at 1 minute and every 5 minutes during the procedure. Also, additional fentanyl consumption, oxygen support requirements, time for recovery room discharge, adverse effects, and patient satisfaction were recorded.. The mean blood pressure, heart rate, and SpO(2) values were significantly lower in group I at 5 and 10 minutes (P < .01). The mean visual analogue scale scores and fentanyl consumption were higher in group I (P < .001). The additional meperidine requirement was higher in group I (P = .014). In group I, oxygen requirement was higher and recovery room period was longer than in the other 2 groups (P < .001), and 2 patients from group I had respiratory depression develop. The incidence of nausea and vomiting was higher in group I (P < .05). The patients' satisfaction scores were higher in groups II and III than in group I (P = .001).. Eight milligrams of intravenously administered lornoxicam 15 minutes before SWL provides pain relief and patient satisfaction during the procedure, reducing opioid requirements as well as decreasing the incidence of side effects.

Topics: Adult; Analgesics; Double-Blind Method; Female; Humans; Injections, Intravenous; Lithotripsy; Male; Middle Aged; Pain; Pain Measurement; Patient Satisfaction; Piroxicam; Treatment Outcome

Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks' treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Drug Administration Schedule; Dyspepsia; Female; Hip Joint; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain; Piroxicam

To perform a chemoreactome modeling of the pharmacological central effects of 4 non-steroidal anti-inflammatory drugs (NSAIDs): dexketoprofen, ketoprofen, aceclofenac, lornoxicam.. An analysis of the pharmacological spectrum of the central action of dexketoprofen, ketoprofen, aceclofenac and lornoxicam was based on the chemoinformatic approach, which compared drug-likeness properties with public and commercial software.. The effectiveness of NSAIDs is related to the inhibition of cannabinoid receptors CB-1, the vanilloid receptor TRPV1, NMDA and AMPA receptors and of the GABA reuptake transporter, with dexketoprofen being the most effective inhibitor. The safety of the central effects of NSAID is due to weak interactions of the NSAIDs studied with opioid, adrenergic, serotonin and dopamine receptors. Chemoreactome modeling made it possible to compare the particulars of the effects of the studied NSAIDs on experimental pain and cramps.. Inhibition of CB-1, TRPV1, NMDA, AMPA, GABA transporter by the NSAID molecules corresponds to a decrease in the intensity of nociceptive signals. A weak intervention of the studied NSAIDs in opioid, adrenergic, serotonin and dopaminergic neurotransmission corresponds to a decrease in the central side-effects of NSAIDs and to a lessened antagonism of these NSAIDs towards exogenous and endogenous opioids.. Цель исследования. Хемореактомное моделирование у крыс фармакологических центральных эффектов нестероидных противовоспалительных препаратов (НПВП): декскетопрофена, кетопрофена, ацеклофенака, лорноксикама. Материал и методы. Анализ фармакологического спектра центрального действия декскетопрофена, кетопрофена, ацеклофенака и лорноксикама был проведен на основе хемоинформационного подхода, т.е. сравнения эффективности исследуемых молекул с определенной химической структурой со структурами других молекул, для которых молекулярно-фармакологические свойства уже установлены. Результаты. Эффективность центрального действия НПВП обусловлена ингибированием рецепторов каннабиноидов СВ-1, ваниллоидного рецептора TRPV1, NMDA- и AMPA-рецепторов и транспортера обратного захвата γ-аминомасляной кислоты (ГАМК), причем наиболее эффективным ингибитором являлся декскетопрофен. Безопасность центральных эффектов обусловлена слабыми взаимодействиями исследованных НПВП с опиоидными, адренергическими, серотониновыми и дофаминовыми рецепторами. Хемореактомное моделирование позволило сравнить особенности действия исследованных НПВП на боль и судороги. Заключение. Ингибирование молекулами НПВП рецепторов СВ-1, TRPV1, NMDA, AMPA и ГАМК-транспортера соответствует снижению интенсивности ноцицептивных сигналов. Слабое вмешательство исследованных НПВП в опиоидную, адренергическую, серотониновую и дофаминергическую нейротрансмиссию соответствует снижению центральных побочных эффектов НПВП и меньшему антагонизму этих НПВП с экзогенными и эндогенными опиоидами.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Ketoprofen; Opiate Alkaloids; Pain; Piroxicam

Ethosomes, a novel type of percutaneous drug delivery carrier with a lipid bilayer structure, penetrate the skin barrier due to their deformability and malleability, and presence of ethanol that fluidizes lipids in the skin. In order to further enhance the delivery of drugs through the skin, penetration enhancers are widely used.. The objective of this work was to develop an optimized formulation of lornoxicam ethosomal gels, investigate skin permeability with the addition of penetration enhancers, and evaluate the invivo pharmacodynamics of these formulations.. Lornoxicam ethosomes were prepared by the ethanol injection method and optimized using the orthogonal design method. Lornoxicam ethosomal gels with enhancers were prepared and optimized using in-vitro transdermal delivery experiments. Experiments on lornoxicam ethosomal gels containing various enhancers such as azone, menthol, lauryl alcohol, and oleic acid were conducted using vertical Franz diffusion cells to measure the percutaneous permeability of the different formulations. Furthermore, the in-vivo analgesic effects of the optimized lornoxicam ethosomal gels were examined using the hot-plate and acetic acid-induced writhing tests. Anti-inflammatory activity was investigated using the dimethylbenzene-induced mouse ear swelling method.. The results showed that compared to other formulations, the optimized lornoxicam ethosomal gels with 5 % menthol significantly increased transdermal penetration. Meanwhile, the optimized lornoxicam ethosomal gels showed remarkably anti-nociceptive and anti-inflammatory activity compared with the plain lornoxicam gels.. These results suggest that the optimized ethosomal gel formulated in this study is a promising lornoxicam carrier in transdermal delivery systems to enhance anti-nociceptive and antiinflammatory efficiency.

Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholesterol; Drug Compounding; Drug Delivery Systems; Edema; Ethanol; Female; Gels; Hot Temperature; Lecithins; Liposomes; Menthol; Mice, Inbred BALB C; Pain; Piroxicam; Skin Absorption; Xylenes

In the past decade several studies have reported that in some brain areas, particularly, in the midbrain periaqueductal gray matter, rostral ventro-medial medulla, central nucleus of amygdala, nucleus raphe magnus, and dorsal hippocampus, microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. Given this evidence, in this study we investigated the development of tolerance to the analgesic effects of NSAIDs diclofenac, ketorolac and xefocam microinjected into the rostral part of anterior cingulate cortex (ACC) in rats.. Male Wistar experimental and control (saline) rats were implanted with a guide cannula in the ACC and tested for antinociception following microinjection of NSAIDs into the ACC in the tail-flick (TF) and hot plate (HP) tests. Repeated measures of analysis of variance with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluations.. Treatment with each NSAID significantly enhanced the TF and HP latencies on the first day, followed by a progressive decrease in the analgesic effect over a 4-day period, i.e., developed tolerance. Pretreatment with an opioid antagonist naloxone completely prevented the analgesic effects of the three NSAIDs in both behavioral assays.. These findings support the concept that the development of tolerance to the antinociceptive effects of NSAIDs is mediated via an endogenous opioid system possibly involving descending pain modulatory systems.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Tolerance; Gyrus Cinguli; Ketorolac; Male; Microinjections; Naloxone; Narcotic Antagonists; Opioid Peptides; Pain; Piroxicam; Rats, Wistar

To investigate the efficacy of lornoxicam in the prevention of the pain associated with propofol injection.. Approval for this study was granted by the ethics committee of our hospital. Using a computer randomisation software, 120 patients undergoing elective surgery were assigned to four equal groups. In Group I (control group), immediately before anaesthesia induction, 10 ml of isotonic 0.9% NaCl solution (placebo) was administered intravenously (IV). In Groups II, III and IV, the same injection contained 2 mg, 4 mg and 8 mg of lornoxicam respectively. A tourniquet was then applied to the forearm for two minutes. Pain evaluation was made using a verbal pain score.. Differences in pain severity scores were statistically significant between Groups I and II, Groups I and III, Groups I and IV and between Groups II and III (p < 0.05). However, no significant difference was determined between Groups III and IV (p = 0.401).. In all groups administered with lornoxicam, there was a significant reduction in the severity of pain associated with propofol injection, in comparison with the control group. Maximum effect is obtained with a dose of 4 mg.

Topics: Administration, Intravenous; Adult; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Piroxicam; Propofol; Random Allocation; Software; Treatment Outcome

To assess the safety of lornoxicam with particular focus on gastrointestinal (GI) events.. Data on adverse drug reactions (ADRs) were pooled from 60 comparative studies of lornoxicam.. A total of 6420 patients received lornoxicam, 1192 received placebo and 3770 received a comparator analgesic. ADRs were reported by 21% of lornoxicam-treated patients, with GI events the most frequent (14 vs 8% with placebo). Across 15 studies that compared lornoxicam (n = 1287) with another NSAID (n = 1010), there was a reduced risk of a GI ADR with lornoxicam (0.78 [95% CI: 0.64-0.96]; p = 0.017).. Lornoxicam was well tolerated with the type of GI events observed consistent with the known safety profile of NSAIDs.

Topics: Adult; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase Inhibitors; Female; Gastrointestinal Diseases; Humans; Male; Middle Aged; Pain; Piroxicam; Treatment Outcome

Oro-dental diseases are generally associated with pain that is controlled using oral tablets containing NSAIDs. Lornoxicam, a relatively new NSAID, is effective in relieving pain accompanying different oro-dental problems. The aim of the current research is to prepare oro-dental analgesic and anti-inflammatory gel using provesicular approach to deliver lornoxicam directly to the site of action in the oral cavity. Local administration of lornoxicam is expected to be superior to systemic delivery in pain relieving and poses less GIT adverse effects. Different surfactants were utilized to prepare the proniosomal gels that rapidly transform into nano-sized niosomes after hydration with the oral saliva. The effect of the surfactant structure on vesicles size distribution and entrapment efficiency percentage (EE%) was investigated. The proniosomal formulations were incorporated into carbopol hydrogels that were characterized regarding rheological and mucoadhesion properties. Moreover, ex-vivo mucosal membrane permeation studies were conducted for selected proniosomal gels to quantify the permeation parameters and assess the amount of drug deposited within the oral mucosa. Results revealed that mucoadhesive proniosomes formulation prepared using Span 60 was optimal as it was nano-sized and also showed the highest EE%. The transmucosal flux of lornoxicam, from these proniosomal formulations, across the oral mucosa was significantly higher (p < 0.05) than lornoxicam containing carbopol gel and the percent drug diffused increased more than twofolds. The results collectively suggest that the mucoadhesive proniosomal gels can be assertively considered as a promising carrier for transmucosal delivery of lornoxicam into the oral cavity.

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Candidiasis, Oral; Gels; Humans; Liposomes; Molecular Structure; Pain; Piroxicam; Surface-Active Agents

Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsion (NE) of lornoxicam (LRX) were prepared for the treatment of painful and inflammatory conditions of the skin. Compritol® 888 ATO, Lanette® O and oleic acid were used as solid and liquid lipids. SLN, NLC and NE were found physically stable at various temperatures for 6 months. Case I diffusional drug release was detected as the dominant mechanism indicating Fickian drug diffusion from nanoparticles and nanoemulsion. The highest rate of drug penetration through rat skin was obtained with NE followed by NLC, SLN and a gel formulation. Nanoformulations significantly increased drug penetration through rat skin compared to the gel (p<0.05). Thus, SLN, NLC and NE of LRX can be suggested for relieving painful and inflammatory conditions of the skin.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Carriers; Drug Liberation; Drug Stability; Drug Storage; Emulsions; Fatty Acids; Fatty Alcohols; Inflammation; Lipids; Male; Nanoparticles; Oleic Acid; Pain; Piroxicam; Rats; Rats, Wistar; Skin Absorption; Skin Diseases; Temperature; Time Factors

Pain is characterized as a complex experience, dependent not only on the regulation of nociceptive sensory systems, but also on the activation of mechanisms that control emotional processes in limbic brain areas such as the amygdala and the hippocampus. Several lines of investigations have shown that in some brain areas, particularly the midbrain periaqueductal gray matter, rostral ventro-medial medulla, central nucleus of amygdala and nucleus raphe magnus, microinjections of non-steroidal anti-inflammatory drugs (NSAIDs) induce antinociception with distinct development of tolerance. The present study was designed to examine whether microinjection of NSAIDs, clodifen, ketorolac and xefocam into the dorsal hippocampus (DH) leads to the development of antinociceptive tolerance in male rats.. The experiments were carried out on experimental and control (with saline) white male rats. Animals were implanted with a guide cannula in the DH and tested for antinociception following microinjection of NSAIDs into the DH in the tail-flick (TF) and hot plate (HP) tests. Repeated measures of analysis of variance with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluations.. We found that microinjection of these NSAIDs into the DH induces antinociception as revealed by a latency increase in the TF and HP tests compared to controls treated with saline into the DH. Subsequent tests on days 2 and 3, however, showed that the antinociceptive effect of NSAIDs progressively decreased, suggesting tolerance developed to this effect of NSAIDs. Both pretreatment and post-treatment with the opioid antagonist naloxone into the DH significantly reduced the antinociceptive effect of NSAIDs in both pain models.. Our results indicate that microinjection of NSAIDs into the DH induces antinociception which is mediated via the opioid system and exhibits tolerance.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Diclofenac; Drug Resistance; Hippocampus; Ketorolac; Male; Microinjections; Naloxone; Narcotic Antagonists; Pain; Piroxicam; Rats; Rats, Wistar

Our recent investigations have shown that microinjection of three non-steroidal anti-inflammatory drugs (NSAIDs) analgin, ketorolac and xefocam into the central nucleus of amygdala produce tolerance to these drugs and cross-tolerance to morphine. We have observed the same phenomenon in midbrain periaqueductal grey matter and nucleus raphe magnus. The medullar nucleus raphe magnus (NRM) is one of important parts of CNS circuit that controls nociceptive transmission at the level of spinal cord. It is functionally involved in descending pain modulation, and mainly consists of serotoninergic neurons. The aim of this study was to examine opioid sensitivity of NSAIDs action in NRM of male rats. For this purpose 30 minutes later of NSAIDs administrations we microinjected μ-opioid antagonist naloxone and tested rats for tail flick and hot plate latencies. Our investigation showed that microinjection of naloxone in NRM significantly decreased antinociceptive effects of NSAIDs at the first day in the TF and HP latencies. At the second day, naloxone generally had trend effects in both TF and HP tests. These results strongly support the suggestion on endogenous opioid involvement in NSAIDs antinociception and tolerance. On the other hand, our evidence confirms once more that NRM is involved in the descending pain control circuit inhibiting spinal nocifensive reflexes.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dipyrone; Drug Interactions; Drug Tolerance; Ketorolac; Male; Microinjections; Morphine; Naloxone; Nociceptors; Pain; Periaqueductal Gray; Piroxicam; Raphe Nuclei; Rats; Spinal Cord

Topics: Analgesics; Double-Blind Method; Humans; Kidney Calculi; Lithotripsy; Pain; Piroxicam; Randomized Controlled Trials as Topic; Retreatment; Treatment Failure

To investigate the anti-inflammatory effect of preemptive intrathecal Lornoxicam on foot swelling of formalin test in rats.. Eighteen healthy male adult Sprague-Dawley (SD) rats (about 250 g) were randomized into 3 groups: intrathecal solvent group (group S, solvent 20 microL), intramuscular Lornoxicam group (group IM, Lornoxicam 300 microg/20 microL) and intrathecal Lornoxicam group (group IT, Lornoxicam 300 microg/20 microL). After measuring the basic volumes of the left hind paws, rats were injected with corresponding solution intrathecally or intramuscularly, and followed by an intra-plantar administration of 100 microL of 5% formalin 10 minutes later. The volumes of left hind paws were measured again at 10 min, 30 min, 1 h, 2 h, 3 h, 4 h, 24 h after formalin injection.. There was no statistical difference of weights or basic volumes among three groups. At 10 min after formalin injection, the left hind paw volume of group IT [(1.53 +/- 0.06) mL] were smaller than that of group S [(1.67 +/- 0.09) mL], P=0.039, but there was no statistically difference between group IT and group IM [(1.65 +/- 0.06) mL]. At 30 min after formalin injection, the left hind paw volume of group S [(1.88 +/- 0.88) mL] was larger than that of group IM [(1.77 +/- 0.05) mL, P<0.05] and group IT [(1.61 +/- 0.06) mL, P<0.01]. The feet swelling degree of group IT was less than that of group IM, P<0.05. At 1 h, 2 h and 3 h after formalin injection, the left hind paw volume of group S was similar to that of group IM, and the volume of group IT was smaller than the other two groups. At 4 h and 24 h after formalin injection, there were no statistic differences of the left hind paw volume among the three groups.. At 10 min to 3 h after formalin injection, swelling of rat feet induced by formalin was alleviated by preemptive intrathecal Lornoxicam.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Foot Diseases; Formaldehyde; Injections, Spinal; Male; Pain; Piroxicam; Random Allocation; Rats; Rats, Sprague-Dawley

The objective of this study was to investigate an antinociceptive effect of preemptive intrathecal lornoxicam on behavior and expression of c-Fos protein in the spinal cord of the formalin hurting rats.. Forty-two healthy male adult SD rats (200-250 g) were randomized into 7 groups. In the normal saline control group (group NS), 20 microL of normal saline was injected intrathecally, which was followed by a subcutaneous administration of 100 microL of normal saline into the hind plantar skin of rats 10 min later. In the formalin control group (group FOR), 20 microL of normal saline was injected intrathecally, and followed by rat intraplantar administration of 100 microL of 5% formalin. In the intrathecal lornoxicam experiment groups (groups L60-300), lornoxicam 60, 120, 180, 240, and 300 micdrog were administered intrathecally, respectively, and followed by rat intra-plantar administration of 100 microL of 5% formalin. The graded pain behavior was observed and the nociceptive behavior index (NBI) was calculated per 5 min during one hour immediately after the intra-plantar injection. At the 2-hour time point, all the rats were deeply anesthetized and perfused intracardially; and then, the spinal cord was removed for analysis of c-Fos protein-like immunoreactive neurons (FLIN) at the dorsal horn in the L4-L6 segments. The Student-Newman-Keuls test was used to identify the differences between groups,and correlation analysis was used to demonstrate the relationship between rat behavior and c-Fos expression.. Almost no pain response was observed in group NS. The typical biphasic pain response was observed in the formalin-injected groups. In phase I, no difference in the NBI was found between the formalin-injected groups except group L240 and group L300 in which NBI were significantly smaller than that in other formalin-injected groups. In phase II, the cumulative NBI in phase II decreased with the increase in lornoxicam dosage, but the difference was not significant when the dosage above 180 microg. (2) Both in the superficial and deep laminae at the dorsal horn, the amount of FLIN of group NS was much less than that of the remaining groups. The amount of FLIN decreased with the increase in the lornoxicam dosage, but the difference was not significant when the dosage above 180 microg in the superficial lamina and above 240 microg in the deep lamina. (3) Correlation analysis showed that the correlation coefficient between the sum of NBI in one hour and the expression of c-Fos in the superfacial or deep lamina of dorsal horn was positive.. Pre-intrathacal lornoxicam can successfully inhibit nociceptive behavior and c-Fos expression in spinal dorsal horn of formalin test rats. This effect is correlated with the dosage of lornoxicam and has ceiling phenomenon.

Topics: Analgesics; Animals; Formaldehyde; Male; Pain; Pain Measurement; Piroxicam; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Spinal Cord

We aimed to determine the analgesic efficacy and clinical or histopathological neurotoxicity of epidural single-dose lornoxicam. Caudal epidural catheters were inserted into 28 rabbits, divided into four groups, on day 1. Pain latency and degree of motor and sensory loss for each animal for different concentrations of lornoxicam were determined on day 2. All animals were sacrificed on day 3 and laminectomy was performed. Five-mum thick sections of spinal cord, obtained from two segments caudal and two segments rostral from tip of the catheter, were fixed and were stained and evaluated by light microscopy. Lornoxicam produced dose-dependent analgesia (increase in pain latency), brief, mild and reversible motor and sensory block, and histopathological signs of neurotoxicity. Clinical application of epidural lornoxicam should proceed with caution.

Topics: Analgesia, Epidural; Anesthesia, Spinal; Animals; Anti-Inflammatory Agents, Non-Steroidal; Catheterization; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Pain; Pain Measurement; Pain Threshold; Pain, Postoperative; Piroxicam; Rabbits; Reaction Time; Sensation Disorders; Spinal Cord

To investigate analgesic actions after local peripheral administration of Lornoxicam in an animal model of formalin test.. Male Spague-Dawley rats were randomly divided into 3 groups, namely the control, the ipsilateral and the contralateral groups. Each group consisted of 8 rats. Thirty minutes prior to subcutaneous injections of 20 g/L formalin 50 microl into the plantar surface of the right hind-paw, the rats of ipsilateral group received Lornoxicam in the plantar surface of the right hind-paw, and the rats of contralateral group received Lornoxicam in the contralateral plantar surface of the hindpaw. Pain response was recorded for a period of 60 minutes. The summation of time (in seconds) spent in licking and biting responses to the injected paw during each 5 minutes block was analyzed for comparison.. The pain response in the first phase (from 0 to 10 minutes) was not inhibited (P > 0.05). The pain response in the second phase (from 10 to 60 minutes) was inhibited in the ipsilateral group (P < 0.05).. Local peripheral administration of Lornoxicam has analgesic effect on the rat's planta in the second phase of a formalin test model; the mechanism involved is mainly local, but not systemic.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Formaldehyde; Male; Nociceptors; Pain; Pain Measurement; Piroxicam; Random Allocation; Rats; Rats, Sprague-Dawley

Transdermal nitroglycerine can improve analgesic effects when used with other analgesics. The aim of the study was to investigate the additive effects of nitroglycerine combined with lornoxicam for acute pain in rats. Thirty-nine Wistar male rats were divided into five groups; Group SF (n=8, saline), Group L-1 (n=8, lornoxicam 1.3 mg/kg), Group L-2 (n=8, lornoxicam 2.6 mg/kg), Group LNO (n=8, nitroglycerine and lornoxicam, 1 mg/kg+1.3 mg/kg), and Group LNO-2 (n=8, nitroglycerine and lornoxicam, 1 mg/ kg+2.6 mg/kg). Tail flick and hot plate tests were measured in all groups before the intraperitoneal injections of drug and 30, 60 and 90 minutes after the injections. Cut-off time was 20 s and 60 s in tail-flick and hot-plate tests. Although there were significant differences between the groups according to hot-plate test at the 30th, 60th and 90th minutes (p<0.05), there was no difference between the groups with tail flick test. The most increasing of latency response in hot-plate assays was seen in Group LNO-1 compared to other groups at the 30th minute (p<0.05). The latency response increased significantly in Group L-1, L-2, LNO-1 and LNO-2 compared with saline group at the 60th and 90th minutes (p<0.05). There were significant differences in latency responses in Group L-1 and Group LNO-1 compared to Group L-2 and Group LNO-2 at the 60th and 90th minutes. In conclusion, 1.3 mg/kg dose of lornoksicam with the use of nitrogliserine provided early and efficient analgesia, but the increasing dose of lornoksicam did not maintain better analgesia.

Topics: Acute Disease; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Therapy, Combination; Hot Temperature; Injections, Intraperitoneal; Male; Nitroglycerin; Pain; Pain Measurement; Piroxicam; Rats; Rats, Wistar