buprenorphine and Body-Weight

Managing postoperative pain in rodents is an important part of any animal care and use program, and identifying an optimal analgesic plan for a surgical procedure is critical to providing for animal welfare. Opioids and NSAID are commonly used in rodents, but few studies have evaluated their efficacy in surgical models. The current study aimed to evaluate the therapeutic efficacy of clinically relevant doses of buprenorphine (2 formulations) or meloxicam used in combination with ketamine and xylazine anesthesia in a Sprague-Dawley rat ovariohysterectomy surgical model. Rats received either subcutaneous saline once daily for 3 d, low-dose (0.05 mg/kg SC) or high-dose (0.1 mg/kg SC) buprenorphine twice daily for 3 d, a single injection of sustained-release buprenorphine (1.2 mg/kg SC), or low-dose (1 mg/kg SC) or high-dose (2 mg/kg SC) meloxicam once daily for 3 d. Clinical analgesic efficacy was assessed over 8 d according to cageside observation scoring, body weight, and behavioral testing. Ovariohysterectomy was associated with 2 d of postoperative pain, and all 3 buprenorphine dosing strategies and both doses of meloxicam demonstrated varying amounts of analgesia. Given the results of the current study, we recommend 0.05 mg/kg SC buprenorphine at least twice daily or a single dose of 1.2 mg/kg SC of sustained-release buprenorphine for rats undergoing midline laparotomy with ovariohysterectomy. Alternatively, meloxicam at 1 to 2 mg/kg SC once daily could be used for this indication.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Female; Laboratory Animal Science; Laparotomy; Meloxicam; Pain Measurement; Pain, Postoperative; Rats; Rats, Sprague-Dawley

Among the many analgesic agents available, buprenorphine appears to be the analgesic used most often in rabbits. Unfortunately, deleterious side effects of opioids, such as gastrointestinal stasis and anorexia, may discourage the use of these agents. Methylnaltrexone is a peripheral opioid antagonist that ameliorates opioid-induced gastrointestinal stasis in others species yet preserves the analgesic effects of buprenorphine. We evaluated whether methylnaltrexone reversed buprenorphine-induced gastrointestinal stasis in 8 healthy male New Zealand White rabbits. To measure gastrointestinal transit time, each rabbit received 20 barium-filled spheres through an orogastric tube. Rabbits then received 4 treatments in random order: buprenorphine (0.05 mg/kg SC), methylnaltrexone (1 mg/kg SC), both agents combined (B+M), or normal saline (control) every 12 h for 2 d. Fecal production was measured every 6 h, and water and food consumption, and body weight, were measured daily, for 5 d after each treatment. The time to appearance of the first sphere was significantly longer for buprenorphine group than for control and methylnaltrexone groups. Daily fecal output was lowest for buprenorphine and B+M, intermediate for control, and highest for methylnaltrexone. Water and food consumption were lower for groups buprenorphine and B+M than for control and methylnaltrexone. Body weight was not affected. In conclusion, treatment with buprenorphine 0.05 mg/kg BID for 2 d in healthy rabbits decreased food and water consumption, prolonged gastrointestinal transit time and decreased the fecal output. Coadministration of methylnaltrexone at 1 mg/kg did not alleviate these negative side effects.

Topics: Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Drug Therapy, Combination; Feces; Gastrointestinal Transit; Laboratory Animal Science; Male; Naltrexone; Narcotic Antagonists; Quaternary Ammonium Compounds; Rabbits

This study compared the efficacy of buprenorphine, carprofen, and a combination of the 2 analgesics in female baboons. Physiologic and behavioral parameters were assessed at baseline and postoperatively for 6 d by use of continuous noninvasive physiologic monitoring and twice-daily videotaping. Prior to surgery, all animals received a pre-emptive dose of either 0.01 mg/kg buprenorphine intramuscularly, 2.2 mg/kg carprofen intramuscularly, or a combination of 0.01 mg/kg buprenorphine and 2.2 mg/kg carprofen intramuscularly. All animals in the carprofen (n = 4) and buprenorphine+carprofen (n = 4) treatment groups appeared to have sufficient analgesia. Three of 4 animals in the buprenorphine group had adequate analgesia. The fourth animal had an elevated heart rate and spent less time standing during the postoperative period. In this study, the use of carprofen or a combination of carprofen plus buprenorphine provided more reliable postoperative analgesia than buprenorphine alone.

Topics: Analgesics; Animals; Body Weight; Buprenorphine; Carbazoles; Drug Therapy, Combination; Feeding Behavior; Female; Hydrocortisone; Pain Measurement; Pain, Postoperative; Papio anubis

This study was carried out to determine an effective regimen for pain management in streptococcal cell wall (SCW)-induced arthritis in female Lew/SSN rats. Forty weanling rats lin 2 groups) were trained to accept disks of jelly as part of their dietary regimen. At 8 weeks of age weighing 150 g, SCW arthritis was induced and sublingual buprenorphine tablets were incorporated into the jelly disks to alleviate the pain of acute arthritis, which developed 24 h post-induction. Group A rats received buprenorphine at a rate of 1 mg/kg 12 hourly. Group B rats received buprenorphine at a rate of 2 mg/kg 12 hourly. Both groups of rats were monitored for symptoms of distress using an adaptation of the Morton and Griffin scale of adverse reactions. Group A rats with severe arthritis required additional subcutaneous (s.c.) injections of buprenorphine to alleviate the adverse effects of arthritis. Group B rats, with twice the dose of buprenorphine did not require additional s.c. injections of buprenorphine. Histological sections of rat hocks indicated that the inflammation was suppressed in Group B rats. We concluded that oral administration of buprenorphine is an effective method of pain management in the pathogenesis of SCW-induced arthritis in Lew/SSN rats. In this model of arthritis, oral buprenorphine has a significant anti-inflammatory effect and appears to modulate the destructive arthritic phase in joints in this animal model of arthritis.

Topics: Administration, Sublingual; Animals; Anti-Inflammatory Agents; Appetite; Arthritis; Body Weight; Buprenorphine; Female; Palliative Care; Polysaccharides, Bacterial; Rats; Rats, Inbred Lew; Rodent Diseases

Total intravenous anesthesia (TIVA) has been recommended in view of avoiding air pollution. However, intermittent administration of anesthetic agents has a large disadvantage of delayed emergence. We reported that continuous TIVA with propofol, ketamine, vecuronium and buprenorphine (PKBp) could bring rapid emergence. In this study, we calculated and compared the cost of anesthesia in the subjects who had undergone general anesthesia either with continuous PKBp or nitrous oxide-oxygen-sevoflurane. In group PKBp subjects, after induction with propofol, ketamine, vecuronium and buprenorphine, anesthesia was maintained with continuous intravenous administration of propofol corresponding to the patient's age using twice step down method; ketamine (240 micrograms.kg-1.h-1), vecuronium (80 micrograms.kg-1.h-1) and buprenorphine (0.4 microgram.kg-1.h-1). Group GOS subjects, after the same induction method, received nitrous oxide, sevoflurane and vecuronium. Moreover, the group GOS subjects were divided to two groups; the high flow GOS (N2O:O2:sevoflurane = 4 l:2 l:30 ml) and the low flow GOS (N2O:O2:sevoflurane = 2 l:1 l:15 ml). Continuous PKBp group showed lower cost than the high flow GOS group. The PKBp group showed lower cost than the low flow GOS group except in patients weighing more than 100 kg. Furthermore, we calculated the cost of continuous PKBp anesthesia in Japan, U.S.A. and U.K. The U.S.A. cost of PKBp was higher than the Japanese and the U.K., because the cost of ketamine in U.S.A. is higher than in the other countries. Continuous PKBp is more economical than the high flow GOS, and continuous PKBp in Japan is more economical than in U.S.A.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Anesthesia Recovery Period; Anesthesia, General; Anesthesia, Intravenous; Anesthetics, Intravenous; Body Weight; Buprenorphine; Child; Child, Preschool; Cost-Benefit Analysis; Humans; Infant; Japan; Ketamine; Middle Aged; Propofol; Vecuronium Bromide

Buprenorphine (0.1, 0.2, 0.3 or 0.4 mg/kg) in a flavoured gelatin base was administered preoperatively to rats undergoing a flank laparotomy. A control group of animals underwent surgery and received only flavoured gelatin. Body weight loss was significantly greater in the group which received no analgesia than in any of the analgesic-treated groups (P < 0.01). Food consumption was reduced significantly in all groups except in those animals which received 0.3 mg/kg buprenorphine. Water consumption was significantly reduced in the control (no analgesia) group (P < 0.001), but was not significantly depressed in the analgesic-treated groups (P > 0.05). Between-group comparisons did not show any significant difference between the different dose rates of analgesia used on either the change in body weight or the reduction in food or water consumption. The results of this study support the use of buprenorphine jelly for post-surgical analgesia in rats. This route of delivery is easy to use, and causes a minimum of stress to the rats.

Topics: Administration, Oral; Analgesia; Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Drinking; Eating; Female; Gelatin; Laparotomy; Pain, Postoperative; Preoperative Care; Rats; Rats, Wistar; Specific Pathogen-Free Organisms; Stomach

Complete Freund's adjuvant (CFA)-induced arthritis in rats is a common animal model for studying chronic inflammatory pain. However, modelling of the disease is associated with unnecessary pain and impaired animal wellbeing, particularly in the immediate post-induction phase. Few attempts have been made to counteract these adverse effects with analgesics. The present study investigated the effect of buprenorphine on animal welfare, pain-related behaviour and model-specific parameters during the disease progression in a rat model of CFA-induced monoarthritis. The aim was to reduce or eliminate unnecessary pain in this model, in order to improve animal welfare and to avoid suffering, without compromising the quality of the model. Twenty-four male Sprague Dawley rats were injected with 20 μl of CFA into the left tibio-tarsal joint to induce monoarthritis. Rats were treated with either buprenorphine or carprofen for 15 days during the disease development, and were compared to a saline-treated CFA-injected group or a negative control group. Measurements of welfare, pain-related behaviour and clinical model-specific parameters were collected. The study was terminated after 3 weeks, ending with a histopathologic analysis. Regardless of treatment, CFA-injected rats displayed mechanical hyperalgesia and developed severe histopathological changes associated with arthritis. However, no severe effects on general welfare were found at any time. Buprenorphine treatment reduced facial pain expression scores, improved mobility, stance and lameness scores and it did not supress the CFA-induced ankle swelling, contrary to carprofen. Although buprenorphine failed to demonstrate a robust analgesic effect on the mechanical hyperalgesia in this study, it did not interfere with the development of the intended pathology.

Topics: Analgesics, Opioid; Animals; Ankle Joint; Arthritis, Experimental; Behavior, Animal; Body Weight; Buprenorphine; Carbazoles; Corticosterone; Disease Models, Animal; Facial Pain; Freund's Adjuvant; Hyperalgesia; Male; Rats; Rats, Sprague-Dawley

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.

Topics: Animals; Animals, Newborn; Body Weight; Buprenorphine; Delayed-Action Preparations; Female; Male; Pain, Postoperative; Rats; Rats, Sprague-Dawley; Sex Characteristics; Skin Temperature

Topics: Analgesics, Opioid; Animals; Body Weight; Brain; Buprenorphine; Female; Fetus; Male; Maternal-Fetal Exchange; Methadone; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley

In guinea pigs, studies addressing the efficacy, safety, and pharmacokinetic profiles of different sustained-release buprenorphine (SRB) formulations are still in their infancy. Here we assessed the pharmacokinetic profiles of 3 SRB dosages (SR-LAB, ZooPharm; SRBLow, 0.15 mg/kg; SRBMedium, 0.3 mg/kg; and SRBHigh, 0.6 mg/kg) for 72 h after a single subcutaneous administration to 8 (4 male and 4 female) healthy guinea pigs. Body weight, fecal output, and cortisol levels were also monitored and the results compared with those of the sham group. Within the first h after administration, the maximal plasma concentration (Cmax) of the drug was 64.3 ± 9.2 ng/mL (males) and 71.3 ± 3.7 ng/mL (females) in the SRBHigh group; 11.5 ± 3.2 ng/mL (males) and 6.9 ± 0.9 ng/mL (females) in the SRBMedium group; and 2.3 ± 0.8 ng/mL (males) and 2.0 ± 0.5 ng/mL (females) in the SRBLow group. After 72 h, therapeutic levels of the drug (>1 ng/mL) were observed only in guinea pigs treated with SRBHigh (both sexes) and males treated with SRBMediu cm. Fecal output (quantity and distribution) and body weight were significantly lower in the SRB groups as compared with the sham group, and with the SRBHigh group showing larger reductions. Baseline levels of serum cortisol in healthy females (1440 ± 106 ng/mL) were significantly greater than in males (550 ± 66 ng/mL). But, independent of the sex, SRB administration significantly reduced those levels. In conclusion, the data indicate that all 3 SRB dosages can be safely used in guinea pigs. However, therapeutic levels of the drug were observed for at least 48 h only guinea pigs treated with SRBHigh and SRBMedium. Further investigation is needed to determine if these dosages can alleviate pain in guinea pigs.

Topics: Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Delayed-Action Preparations; Female; Guinea Pigs; Hydrocortisone; Male; Pain Management; Pain Measurement; Specific Pathogen-Free Organisms

Extended-release buprenorphine is an effective analgesic in laboratory animals, and its safety has been established in mice but not in rats. The authors used a target animal safety trial to evaluate the safety of extended-release buprenorphine in rats. Fischer 344 rats received post-surgical subcutaneous injections of 1.3 mg, 3.9 mg or 6.5 mg buprenorphine per kg body weight (two times, six times or ten times the intended dose, respectively), and their body weight, clinical signs and symptoms, clinical pathology and histopathology were monitored for 4 d. Body weight was not significantly different in rats that received buprenorphine compared with control rats. Signs of nausea-related behavior were observed in 25% of the rats treated with buprenorphine. Clinical pathology results for all rats were normal, and gross and microscopic histopathology examinations identified no substantial abnormalities, suggesting that this behavior was of minor consequence. Other adverse events previously reported to occur with opiate therapy, including weight loss and dermal lesions at drug injection sites, were not observed in this study. The results of this study show that post-surgical administration of an extended-release buprenorphine product is safe in Fischer 344 rats and does not necessarily cause substantial adverse effects, confirming that opiate therapy is a viable choice in laboratory animal medicine.

Topics: Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Injections, Subcutaneous; Male; Nausea; Postoperative Period; Rats, Inbred F344

Postoperative analgesia in laboratory rats is complicated by the frequent handling associated with common analgesic dosing requirements. Here, we evaluated sustained-release buprenorphine (Bup-SR), sustained-release meloxicam (Melox-SR), and carprofen gel (CG) as refinements for postoperative analgesia. The aim of this study was to investigate whether postoperative administration of Bup-SR, Melox-SR, or CG effectively controls behavioral mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC BID; buprenorphine HCl (Bup HCl), 0.05 mg/kg SC BID; Bup-SR, 1.2 mg/kg SC once; Melox-SR, 4 mg/kg SC once; and CG, 2 oz PO daily. Mechanical and thermal hypersensitivity were tested daily from day-1 through 4. Bup HCl and Bup-SR attenuated mechanical and thermal hypersensitivity on days 1 through 4. Melox-SR and CG attenuated mechanical hypersensitivity-but not thermal hypersensitivity-on days 1 through 4. Plasma concentrations, measured by using UPLC with mass spectrometry, were consistent between both buprenorphine formulations. Gross pathologic examination revealed no signs of toxicity in any group. These findings suggest that postoperative administration of Bup HCl and Bup-SR-but not Melox-SR or CG-effectively attenuates mechanical and thermal hypersensitivity in a rat model of incisional pain.

Topics: Analgesics; Animals; Body Weight; Buprenorphine; Carbazoles; Delayed-Action Preparations; Male; Meloxicam; Pain, Postoperative; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles

The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting a drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains.

Topics: Animals; Antidepressive Agents; Body Weight; Buprenorphine; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Freezing Reaction, Cataleptic; Male; Motor Activity; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Species Specificity; Swimming; Time Factors

Despite the increasing use of rabbits as companion animals and models for biomedical research, rabbits have not been extensively studied to identify an efficacious postsurgical analgesic that does not cause systemic complications. The synergy of NSAID and systemic opioids is well-documented, and their combined use reduces the amount of either drug required for adequate analgesia. We measured fecal corticosterone metabolites (FCM) in rabbits after a minimally invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d), buprenorphine-meloxicam (0.01 mg/kg-0.1 mg/kg SC every 24 h for 3 d), or a single dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3 after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated FCM levels, which continued to rise until day 7 and then gradually returned to baseline by day 28. In the buprenorphine-meloxicam group, FCM was relatively unchanged until day 3, when treatment was discontinued, and then began to rise. Rabbits in the buprenorphine-meloxicam group gained more weight over the 28-d study than did those in the other 3 treatment groups. This study shows that in rabbits low-dose buprenorphine administered with meloxicam effectively mitigates the FCM response that develops after surgery without the adverse effects associated with higher doses.

Topics: Analgesia; Analgesics, Opioid; Anesthetics, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Bupivacaine; Buprenorphine; Corticosterone; Drug Therapy, Combination; Feces; Glucocorticoids; Male; Meloxicam; Minimally Invasive Surgical Procedures; Pain, Postoperative; Rabbits; Thiazines; Thiazoles

Minimizing the pain or discomfort of research animals through refinement of surgical techniques is inherent in the humane use of animals in investigative studies. The current approach for intraperitoneal implantation of radiotelemetry devices in mice is a ventral midline incision. An optional surgical approach is a flank incision. We used multidimensional analysis to compare midline and flank approaches for implantation of radiotelemetry devices in regard to time of surgery, activity, temperature, food intake, gel intake, body weight, and vitality scores. A third group was used to evaluate the effects of buprenorphine in healthy mice. The study demonstrated positive benefits related to the flank approach, including quicker surgery times, improved activity levels, more stable temperature homeostasis, smaller losses in body weight, and quicker return to presurgical baseline levels of food intake. In addition, direct effects of buprenorphine included decreases in food intake and body weight, with the effects on body weight lasting approximately 8 d after treatment. Collectively, these results suggest that implantation of intraperitoneal radiotelemetry devices by using a flank approach is beneficial to mice.

Topics: Analgesics, Opioid; Animals; Body Temperature; Body Weight; Buprenorphine; Drinking; Eating; Laboratory Animal Science; Mice; Multivariate Analysis; Pain, Postoperative; Postoperative Period; Recovery of Function; Surgery, Veterinary; Telemetry

The present study investigated the postoperative plasma concentrations of corticosterone and buprenorphine in male Wistar and Sprague-Dawley rats, treated with buprenorphine administered either through subcutaneous (SC) injection or through voluntary ingestion (VI). The animals were treated with buprenorphine for pre-emptive analgesia prior to surgical placement of a jugular catheter, followed by automated blood sampling during 96 h. Buprenorphine was administered on a regular basis throughout the experiment, and blood was collected on selected time points. Body weight was measured before and 96 h after surgery. It was found that the two rat stocks responded in a similar manner to both buprenorphine treatments, with the exception of body weight change in Wistar rats, in which body weight was reduced after SC treatment. The plasma concentration of corticosterone was significantly higher in the SC-treated animals than in the VI-treated animals during the first 18 h of the study, while plasma buprenorphine concentration was at least as high and more even over time after VI treatment. The present study shows that buprenorphine administration through VI is suitable for both Wistar and Sprague-Dawley rats, with lower stress response and higher plasma concentrations of buprenorphine than after the traditional SC route of administration.

Topics: Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Catheterization; Corticosterone; Jugular Veins; Male; Rats; Rats, Sprague-Dawley; Rats, Wistar; Stress, Physiological

Buprenorphine is administered to humans and animals for postoperative pain management, although its use is associated with complications. Alternative analgesics, including the nonsteroidal antiinflammatory meloxicam, are available, but information on their postoperative effects is limited. The objective of the present study was to compare buprenorphine (0.03 mg/kg SC twice daily for 3 d) with meloxicam (2 mg/kg SC initial dose followed by 1 mg/kg SC once daily for 2 d) by assessing parameters relating to postsurgical recovery in rats that underwent surgical implantation of radiotelemetric transducers. Rats treated after surgery with buprenorphine showed greater reductions in body weight, food consumption, locomotor activity, and nighttime heart rates than did meloxicam-treated rats. Buprenorphine and meloxicam treatments both had stimulatory effects on mean arterial pressure and daytime heart rate measurements, although effects on nighttime mean arterial pressure were greater in the buprenorphine-treated rats. In summary, the lesser physiologic changes associated with meloxicam, as compared with buprenorphine, suggest that meloxicam offers advantages for use as a postoperative analgesic after laparotomy and radiotelemetric transducer implantation in rats.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Buprenorphine; Feeding Behavior; Heart Rate; Male; Meloxicam; Motor Activity; Pain Measurement; Pain, Postoperative; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles; Treatment Outcome

It is essential to identify objective and efficient methods of evaluating postoperative pain in rodents. The authors investigated whether postoperative changes in rates of body weight gain could serve as a measure of the efficacy of meloxicam or buprenorphine analgesia in growing rats. Young adult male Lewis rats underwent general endotracheal anesthesia and thoracotomy and were treated postoperatively for 3 d with saline (no analgesia), buprenorphine (six doses of 0.1 mg per kg) or meloxicam (three doses of 1 mg per kg). The authors evaluated rats' daily growth rates for 5 d after surgery and compared them with baseline (preoperative) growth rates. To discriminate between the effects of postoperative pain and other concurrent physiologic effects associated with anesthesia, thoracotomy or analgesia, the authors evaluated weight changes in multiple control groups. Treatment with buprenorphine in the absence of any other procedure or with anesthesia alone significantly affected rats' body weight. Notably, growth rate was maintained at near normal levels in rats treated postoperatively with meloxicam. These findings suggest that growth rate might serve as an efficient index of postoperative pain after major surgical procedures in young adult rats treated with meloxicam but not in rats treated with buprenorphine.

Topics: Analgesia; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Intubation, Intratracheal; Meloxicam; Pain, Postoperative; Rats; Rats, Inbred Lew; Thiazines; Thiazoles; Thoracotomy; Weight Gain

This study describes the use of allometric scaling in five giant anteaters (Myrmecophaga tridactyla) submitted for osteosynthesis, gastrostomy, or treatment of burns. Chemical restraint was performed by allometric scaling using the dog as a reference; acepromazine (0.06 mg/kg), diazepam (0.3 mg/kg), ketamine (8.8 mg/kg), and buprenorphine (5.9 microg/kg) were combined, and the animals were maintained under isoflurane anesthesia. Heart rate, respiratory rate, hemoglobin oxygen saturation, temperature, and anesthetic depth were measured. Postoperative treatment consisted of ketoprofen, buprenorphine, and ceftiofur. Anesthetic induction was obtained in 10-15 min, achieving muscle relaxation and absence of excitement. Physiologic parameters were stable during the procedures, and postoperative treatment was effective. Allometric scaling was effective for chemical restraint and postoperative treatment.

Topics: Acepromazine; Anesthesia Recovery Period; Anesthesia, Inhalation; Anesthetics, Combined; Animals; Animals, Wild; Body Weight; Buprenorphine; Diazepam; Dose-Response Relationship, Drug; Heart Rate; Ketamine; Mathematics; Respiration; Weights and Measures; Xenarthra

One of the challenges facing veterinarians and investigators who use rabbits (Oryctolagus cuniculus) as a surgical model in biomedical research is choosing an appropriate and efficacious postoperative analgesic without systemic complications and side effects. The objective of this study was to evaluate the gastrointestinal side effects associated with the postoperative use of buprenorphine in Dutch Belted rabbits. We also evaluated the analgesic meloxicam as an alternative to opioid administration during the postoperative period. Rabbits were assigned to 1 of 3 treatment groups during the postoperative period after routine ovariohysterectomy: buprenorphine (n = 10), meloxicam (n = 10), and incisional infiltration with bupivicaine (no treatment control; n = 10). Feed intake, fecal production, weight loss, urine output, and other physiologic parameters were monitored and behavior and pain assessments were performed for 7 d after surgery and compared with baseline values collected before surgery. All rabbits showed decreased pellet consumption, fecal production, and weight on day 1 after surgery. This effect was severe in some rabbits that received bupivicaine; therefore treatment of this entire group with metoclopramide, fluids, and hay was instituted to reverse gut stasis. No significant difference in feed consumption and fecal production was present between the buprenorphine- and meloxicam-treated groups. On the basis of these results, meloxicam appears to be a suitable alternative or adjunct to buprenorphine for alleviating postoperative pain with minimal risk of anorexia and gastrointestinal ileus.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Chemical Analysis; Body Temperature; Body Weight; Buprenorphine; Cyclooxygenase Inhibitors; Meloxicam; Postoperative Period; Rabbits; Thiazines; Thiazoles; Treatment Outcome

Adequate peri-operative analgesia may reduce post-operative stress response and improve recovery in laboratory animals. We have established a method involving repeated automated blood sampling, allowing quantification of serum corticosterone levels in rats for stress assessment without stress-inducing handling or restraint. In the present study, the effects of the commonly used route of buprenorphine administration (0.05 mg/kg injected subcutaneously) were compared with oral administration (0.4 mg/kg mixed with Nutella and orally administered by voluntary ingestion) in male Sprague-Dawley rats.. A catheter was placed in the jugular vein and attached to an Accusampler for automated blood sampling. During 96 h after surgery, blood was collected at specified time points. Pre- and post-operative body weights and water consumption were registered.. Buprenorphine significantly suppressed levels of circulating corticosterone after the oral but not after the subcutaneous treatment. Both buprenorphine treatments had a positive impact on maintenance of body weight and water consumption, compared to the control group that received no buprenorphine.. The present investigation suggests that oral voluntary ingestion ad libitum is an efficacious, convenient and non-invasive way of administering peri-operative buprenorphine to rats, as judged by corticosteroid response and effects on body weight and water consumption.

Topics: Administration, Oral; Analgesia; Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Corticosterone; Drinking; Injections, Subcutaneous; Male; Postoperative Period; Rats; Rats, Sprague-Dawley; Self Administration; Stress, Physiological

Buprenorphine (Bup) is the most commonly used analgesic in mice, yet few objective assessments address its superiority for postsurgical recovery. In mice, IP implantation of a radiotelemetry device induces decreases in body weight (BW), food and water intake (FI, WI), core temperature (Tc), and activity levels that persist approximately 14 d in the absence of analgesia. To compare the efficacy of Bup with that of the nonsteroidal antiinflammatory drug indomethacin (Indo) for postsurgical recovery, male C57BL/6J mice were treated on the day of radiotelemetry implantation with Bup (0.3 mg/kg s.c.) or Indo (1 mg/kg s.c.) followed by treatment with Indo (1 mg/kg p.o.) on the next day (Bup-Indo versus Indo-Indo). Responses were compared between treatments in mice implanted with a radiotelemetry device and those that did not undergo surgery. Changes in BW, FI, WI, Tc, and activity were examined throughout 14 d of recovery. Indo-Indo was more efficacious in inhibiting postsurgical BW, FI, and WI reductions, compared with Bup-Indo. Bup also reduced BW and FI in the absence of surgery, indicating a nonspecific effect of this drug on these variables. Indo-Indo treatment was associated with higher activity levels during lights-on-to-lights-off transition periods compared with that observed with Bup-Indo. According to 5 objective measures of surgical recovery, our data suggest that Indo-Indo treatment is more efficacious than is Bup-Indo for postsurgical recovery of radiotelemetry-implanted mice.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Drinking; Drug Therapy, Combination; Eating; Indomethacin; Laboratory Animal Science; Male; Mice; Mice, Inbred C57BL; Motor Activity; Pain, Postoperative; Recovery of Function; Specific Pathogen-Free Organisms; Telemetry

The goal of the present study was to develop and validate an animal model of unlimited access to intravenous heroin self-administration combined with responding for food and water to characterize the transition to drug dependence. Male Wistar rats were allowed to lever press for heroin (60 microg/kg/0.1 ml infusion/s; fixed ratio 1; 20-s time out) and nosepoke for food and water in consecutive, daily 23-h sessions. Daily heroin intake increased over days, reaching significance by Day 14. Drug-taking increased across the circadian cycle, reflected as increases in both the nocturnal peak and diurnal nadir of heroin intake. Changes in the circadian pattern of food intake and meal patterning preceded and paralleled the changes in heroin intake. By Day 7, the circadian amplitude of feeding was blunted. Nocturnal intake decreased because rats consumed smaller and briefer meals. Diurnal intake increased due to increased meal frequency, whereas total daily food intake decreased. To control for time or experience in the self-administration boxes as a possible confound, rats with saline (no drug) tethers were tested and did not display significant changes in food intake pattern. Body weight gain slowed slightly in heroin rats relative to saline controls. Separate groups of rats revealed that significant physical dependence as measured by physical signs of opiate withdrawal following a naloxone injection (1.0 mg/kg, subcutaneous (s.c.)) was reached by Day 14. Significant increases in heroin intake could be produced using low doses of naloxone (0.003-0.03 mg/kg, s.c.) on days 28-31 of heroin access. After 6 weeks of heroin self-administration, rats injected with buprenorphine (0, 0.01, 0.04, and 0.2 mg/kg, s.c.) showed a dose-dependent reduction in heroin intake. Changes in the pattern of drug and food intake in the present unlimited heroin access model may serve as independent motivational markers for the transition to a drug-dependent state.

Topics: Analgesics, Opioid; Animals; Biomarkers; Body Weight; Brain; Buprenorphine; Circadian Rhythm; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Eating; Feeding Behavior; Heroin; Injections, Intravenous; Male; Motivation; Narcotic Antagonists; Narcotics; Opioid-Related Disorders; Rats; Rats, Wistar; Self Administration; Substance Withdrawal Syndrome

Buprenorphine is a widely used analgesic for relief of postoperative pain in rats. The effect of repeated doses of buprenorphine throughout the postoperative pain and stress response is unknown. This investigation tested the hypotheses that (a) daily analgesic doses of buprenorphine for 7 d ameliorate the stress response after laparotomy in rats and (b) preoperative buprenorphine better ameliorates the response than do peri- and postoperative administration. Postoperative effects on body weight, daily food and water consumption, and daily fecal and urinary outputs were monitored in groups of rats treated for 7 d with analgesic doses of buprenorphine initiated at different time points relative to the time of laparotomy. Analgesic doses of buprenorphine had no effect on the study parameters in healthy unoperated rats. Daily injection of buprenorphine delayed the time at which the preoperative body weight was restored without decreasing the postoperative changes in daily food consumption, water intake, and fecal and urinary outputs in the operated rats. The effects of daily analgesic doses of buprenorphine for 7 d on body weight, daily food, and water consumption, and fecal and urinary outputs were minimal and less statistically significant than the changes caused by surgery itself. However, this dosing regimen seems to delay the restoration of body weight after abdominal surgery in rats.

Topics: Analgesics, Opioid; Animals; Body Weight; Buprenorphine; Digestive System Surgical Procedures; Drug Administration Schedule; Female; Pain, Postoperative; Postoperative Care; Rats; Rats, Wistar

The study examined the efficacy of preemptive or postoperative analgesia on surgical pain in the mouse. Radiotelemetry transmitters were surgically implanted in 28 female ICR mice. A mock ova implantation surgery was then performed. Mice were treated with a single dose of buprenorphine or flunixin meglumine prior to or after surgery, three doses of buprenorphine, or were untreated. Heart rate, blood pressure, home cage activity, food and water consumption, and body weight were measured. The no-analgesia group showed no significant differences between any parameters collected prior to surgery and those collected at similar times during the day of surgery. Significant increases in mouse activity on the day of surgery occurred with all analgesic treatments, compared with pre-surgical activity. There were no consistent significant changes in any other telemetry parameter after treatment with analgesics compared with no analgesia. Food consumption and body weight the day after surgery were reduced significantly in the animals treated with three doses of buprenorphine compared with untreated mice and mice given a single dose of buprenorphine. We conclude that the mock ova implant procedure does not induce sufficient pain to cause alterations in heart rate and blood pressure in the mouse. Activity was significantly reduced in the first 6 h after surgery in mice without analgesia, compared with activity prior to surgery. There were no significant differences between pre-emptive and postoperative analgesia. Body weight and food and water consumption were poor measures of pain because analgesia alone affected these parameters.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Clonixin; Drinking; Eating; Female; Mice; Narcotics; Pain; Postoperative Period; Telemetry

This study evaluated the duration of clinical effects and referred hyperalgesia in rats (n = 10 per group) undergo ing abdominal surgery with analgesics (ketoprofen at 3 mg/kg and buprenorphine at 0.01 or 0.1 mg/kg) administered intramuscularly twice daily for 72 h beginning prior to surgery; no-surgery and no-analgesia control groups were included. Food and water consumption and body weight were monitored daily. As a measure of referred hyperalgesia, tail-flick latency was measured daily, before and 4 h after analgesia administration. Compared with those of the no-surgery controls, significant decreases in food consumption and body weight occurred 24 h after surgery without analgesics. There were nonsignificant reductions in these effects by analgesics, but the benefits were not significantly different than those of saline. These parameters continued to be decreased with variable significance in the buprenorphine groups at 48 and 72 h after surgery. In both buprenorphine-treated groups, water consumption was significantly increased at 24 h after surgery but not at 48 or 72 h. Tail-flick latency was not significantly different between the no-surgery and no-analgesia groups but was significantly increased 4 h after high-dose buprenorphine administration and declined nonsignificantly over time in the other groups. We conclude that painful effects from surgery are present primarily during the first 24 h after surgery. The analgesic regimens tested did not completely reduce these effects. Buprenorphine was associated with adverse effects for as long as 72 h after surgery. Referred hyperalgesia from this abdominal surgery could not be measured using the tail-flick assay.

Topics: Abdomen; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Drinking; Eating; Hot Temperature; Hyperalgesia; Ketoprofen; Pain Measurement; Pain, Postoperative; Rats; Time Factors

The use of mice in biomedical research is increasing, largely due to the production and use of genetically engineered animals. Providing postoperative pain control in mice presents many challenges, and long-acting analgesic preparations would be advantageous for this species. A single subcutaneous injection of a liposome-encapsulated (LE) preparation of oxymorphone was compared with multiple injections of buprenorphine or saline in outbred mice undergoing splenectomy. Control groups were given isoflurane alone or isoflurane and an injection of LE oxymorphone but did not undergo surgery. The following parameters were evaluated for 5 days after surgery and were compared with presurgical baseline data for each group: food and water consumption, body weight, ethographic score, and voluntary exercise on a running wheel. Ethographic scores indicated less postsurgical pain in both groups of mice that received either analgesic preparation compared with mice that received only saline. However, mice given LE oxymorphone had superior postoperative recovery, as measured by wheel-running distance and body weight gain, compared with mice given buprenorphine or saline. Mice undergoing splenectomy had significant decreases in body weight, food and water consumption, voluntary exercise, and other normal behaviors. Administration of liposomal oxymorphone at the time of surgery improved postsurgical recovery as measured by these parameters compared with multiple injections of buprenorphine or saline alone. Administration of LE oxymorphone at the time of surgery improved postsurgical recovery, as measured by these parameters.

Topics: Analgesics, Opioid; Animals; Animals, Outbred Strains; Behavior, Animal; Body Weight; Buprenorphine; Drinking; Eating; Injections, Subcutaneous; Laboratory Animal Science; Liposomes; Male; Mice; Mice, Inbred ICR; Oxymorphone; Pain; Pain Measurement; Physical Conditioning, Animal; Specific Pathogen-Free Organisms; Splenectomy

The objective of this study was to compare the recovery of male rats after a major abdominal surgical procedure (the implantation of a radiotelemetry transmitter) when treated with buprenorphine, butorphanol, or ketoprofen and subcutaneous fluids (5% dextrose) or with subcutaneous fluids only. The parameters for assessing recovery were heart rate (HR), mean arterial blood pressure (MAP), home cage activity, food and water consumption, and body weight. HR, MAP, and activity were continuously monitored by radiotelemetry methods, food and water intakes were determined daily, and body weights were measured once or three times a week. In light of HR, nocturnal home cage activity, water consumption, and body weight gain, animals were recovered by about 7 days after surgery. MAP normalized by 1 to 2 days postsurgery, and food consumption returned to presurgical levels 5 to 12 days after surgery, depending on the analgesic treatment. On the basis of nocturnal activity, HR, and food and water intakes, buprenorphine-treated animals recovered more slowly than did the other two analgesic-treated groups. By the other parameters, all three analgesic-treated groups showed very similar responses across time. Surprisingly, when compared with the groups receiving only subcutaneous fluids, buprenorphine and butorphanol delayed or did not advance recovery, whereas ketoprofen neither retarded nor advanced recovery. Explanations for these results include: (a) the analgesics were effective in relieving pain but had pharmacological side effects that altered the measured parameters, making it difficult to determine recovery; (b) the level of pain experienced did not notably affect recovery; (c) the analgesics, at the doses and/or dosing schedules used, were not effective in the relief of pain, thereby causing both groups of animals to recover at the same rate; and (d) the analgesics interfered with recovery. Final resolution of these issues awaits further investigation.

Topics: Abdomen; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Buprenorphine; Butorphanol; Feeding Behavior; Heart Rate; Ketoprofen; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Time Factors

The objective of this study was to establish effective postoperative analgesia for Dark Agouti rats undergoing liver transplantation with minimal additional stress due to handling and no adverse effect on transplant outcome. Oral administration of buprenorphine (0.5 mg/kg/dose) or aspirin (100 mg/kg/dose) in raspberry-flavoured gelatine were compared to controls receiving no treatment or plain gelatine. The drugs were presented five times: immediately on recovery from anaesthesia and at 12 h intervals thereafter. All rats underwent right nephrectomy and replacement of their liver by an arterialized liver isograft preserved optimally for 24 h. All groups had reversible hepatic damage, lost weight and demonstrated severely reduced dark cycle activity after surgery. Neither treatment appeared to ameliorate the loss of body weight that probably reflected hepatic insufficiency during the first week as well as pain and surgical stress. In the second week, when liver function was 'normal', rats began to regain weight at the pre-transplant rate. Aspirin treatment significantly increased activity during the first and second dark cycles after surgery, whereas buprenorphine significantly increased activity during the second dark cycle only. Neither drug had any apparent adverse effects on the rats or on graft function. Postoperative oral administration of aspirin should be incorporated into future programmes of liver transplantation in rodents. More effective treatment in the immediate postoperative period may require oral administration of analgesia prior to surgery or a single subcutaneous injection of an analgesic agent on completion of surgery in addition to postoperative oral administration of aspirin.

Topics: Activity Cycles; Administration, Oral; Analgesics, Opioid; Animals; Aspirin; Body Weight; Buprenorphine; Creatinine; Female; Hepatectomy; Liver; Liver Function Tests; Liver Transplantation; Male; Motor Activity; Nephrectomy; Postoperative Complications; Rats; Rats, Inbred Strains; Time Factors

The aim of this study was to investigate objective characterisation of gait as a marker of the chronic pain of adjuvant arthritis (AA). Video recorded images of spontaneous rat ambulations were analysed to quantify various temporal and spatial parameters and compare these between the AA and control groups. Changes were also recorded after the administration of a single dose of buprenorphine (15 ?g). Individual temporal parameters were significantly reduced (velocity (P=0.05), stride length (P=0.007), single stance time (P<0.001), swing time (P=0.001)), or increased (dual stance time (P<0.001)) at 10 days in the AA group compared to control. The rear paws showed reduced ground contact and the fore paws an increase in proximal pad and decrease in digit area, although these changes were not all statistically significant. Some of the gait parameters showed significant reversal following administration of buprenorphine (velocity (P<0.001) and stride length (P<0.001) were increased and single stance time (P=0.014) reduced). It is proposed that changes in gait are a marker of AA chronic pain in this model. These behavioural changes were significant at a very early stage (day 10), before the development of physical deformities and increase in paw volume and might permit an earlier detection of pain than other models.

Topics: Analgesics, Opioid; Animals; Area Under Curve; Arthritis, Experimental; Body Weight; Buprenorphine; Chronic Disease; Disease Models, Animal; Female; Freund's Adjuvant; Gait; Hindlimb; Injections, Subcutaneous; Motor Activity; Pain; Pain Measurement; Rats

A retrospective study was performed to determine the influence of age on hemodynamics and awakening time in total intravenous anesthesia (TIVA) with propofol and buprenorphine for spinal surgery. Twenty patients (26-79 yr) were studied and allocated into following four groups by age: 26-49 yr, 50-59 yr, 60-69 yr, and elderly 70-79 yr. All patients were premedicated with midazolam (2.5-5 mg) i.m. Anesthesia was induced (60-180 ml.h-1) and maintained (20-60 ml.h-1) with propofol infusion with 40% oxygen in air, added with vecuronium and one single dose of buprenorphine (0.08-0.2 mg; 1.37-2.63 micrograms.kg-1) before incision. Mean arterial pressure was stable and did not differ in four groups. Heart rate was decreased (P < 0.01) in the elderly group compared with the group younger than 50 yr. Bradycardia (below 50 beat.min-1) occurred in 60% of the elderly group. An adequate dose of buprenorphine (microgram) was proposed as: 208 - 1.8 x age (yr) + 0.3 x weight (kg) (r = 0.90, P < 0.01). The induction and maintenance rates (ml.h-1) of propofol were decreased with age and increased with weight (P < 0.05). However, the maintenance dose of propofol (3.9-8.5 mg.kg-1.h-1) did not correlate with age. Awakening time was prolonged (P < 0.05) in the elderly group (17.0 +/- 7.2 min) as compared with the group of younger than 50 yr (8.0 +/- 3.9 min). The three patients requiring postoperative analgesics were younger than 60 yr. This study suggests that we should reduce the dose of buprenorphine with age in TIVA using propofol. About 50% of the dose given to the patient younger than 50 yr was considered adequate in the elderly group.

Topics: Adult; Aged; Aging; Anesthesia Recovery Period; Anesthesia, Intravenous; Body Weight; Buprenorphine; Female; Hemodynamics; Humans; Intraoperative Period; Male; Middle Aged; Propofol; Retrospective Studies; Spine; Time Factors

The effects of bupivacaine, a long-acting local anaesthetic, and buprenorphine, an opioid analgesic, administered either pre- or post-operatively, were investigated in a rat laparotomy model. Surgical anaesthesia was induced and maintained with halothane. The type of analgesic treatment was a significant factor in the reduction in body weight and food and water intake which occurred following surgery. The largest reductions were seen in the bupivacaine-treated groups and those animals which received no analgesics. The timing of administration of analgesics had no influence on the effect of bupivacaine administration. The group receiving buprenorphine before surgery showed less depression in food intake than the group receiving buprenorphine at the end of surgery. Animals which received buprenorphine showed less depression of activity than those receiving saline or bupivacaine.

Topics: Analgesics, Opioid; Anesthetics, Local; Animals; Body Weight; Bupivacaine; Buprenorphine; Drinking; Eating; Laparotomy; Male; Motor Activity; Pain; Postoperative Care; Preoperative Care; Random Allocation; Rats; Rats, Wistar; Reference Values; Specific Pathogen-Free Organisms

The effects of oral administration of buprenorphine ('buprenorphine jello'), a partial mu opioid agonist, oral naltrexone, a mu antagonist and morphine, a mu agonist, were investigated in rats following laparotomy. Food and water consumption and body weight were reduced in rats that underwent surgery. Rats undergoing anaesthesia alone showed only a small reduction in water consumption. Administration of oral buprenorphine (0.5 mg/kg in flavoured gelatin) decreased the effects of surgery on body weight and water intake when compared to untreated (vehicle alone) controls. The magnitude of this beneficial effect was similar to that seen in previous studies using subcutaneous administration of buprenorphine. The fall in body weight and food and water intake following surgery was similar in the groups which received morphine and the control group which received vehicle (jelly). Neither the magnitude of the fall in body weight, and food and water intake, nor the behavioural scores differed between naltrexone and control (vehicle alone) rats following surgery. This suggests that the beneficial effects of partial agonist analgesics are mediated by a reduction in pain rather than by antagonism of endogenous opioids. Both anaesthesia and surgery caused changes in behaviour, but the major effects of buprenorphine in normal (unoperated) rats severely limited the value of behavioural parameters as a means of assessing possible beneficial effects of analgesic administration.

Topics: Administration, Oral; Analgesics, Opioid; Animals; Behavior, Animal; Body Weight; Buprenorphine; Drinking; Eating; Laparotomy; Male; Morphine; Naltrexone; Narcotic Antagonists; Pain, Postoperative; Rats; Rats, Wistar; Specific Pathogen-Free Organisms

This set of experiments examined the effects of prenatal buprenorphine (BUP) exposure on three measures of sexual differentiation in rats. Pregnant female rats were divided into four treatment groups: 0.6 mg/kg BUP, 0.3 mg/kg BUP, a pair-fed control (PFC), and an untreated control (UTC). Drugs were injected starting on gestation day (GD) 6 and continuing through GD 20 with a 48-h interval between drug administrations. Three variables were examined in the offspring: anogenital (AG) distance on postnatal day (PND) 1, spontaneous parental behavior on PNDs 23-28, and saccharin consumption on PNDs 42-55. Whereas prenatal BUP exposure had no effect on AG distance, spontaneous parental behavior was impaired in the 0.6-mg/kg-exposed offspring on two measures: pup-retrieval latencies and pup-directed behaviors. Furthermore, although both control groups and the 0.3-mg/kg-exposed offspring showed the expected sex difference in consumption of a 0.25% saccharin solution, this difference was not displayed by the 0.6-mg/kg-exposed offspring. These findings suggest that exposure to relatively high doses of buprenorphine during development may have long-term effects on behavior.

Topics: Animals; Behavior, Animal; Body Weight; Buprenorphine; Dose-Response Relationship, Drug; Drinking; Eating; Female; Maternal Exposure; Narcotics; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Characteristics

To determine the cardiovascular effects of buprenorphine in isoflurane- and halothane-anesthetized dogs.. 6 healthy adult hound-type dogs given buprenorphine (16 micrograms/kg of body weight, i.v.) or isovolumetric 5% dextrose solution during anesthesia with isoflurane or halothane.. Each dog was anesthetized 4 times, with a minimum of 10 days between episodes. Anesthesia was induced with isoflurane or halothane in O2 by mask, and was maintained with 1.9% isoflurane or 1.3% halothane (end-tidal concentration). The PaCO2 was maintained between 35 and 45 mm of Hg by use of mechanical ventilation, and the following variables were determined: systolic, diastolic, and mean arterial blood pressures; cardiac output; cardiac index; stroke volume; heart rate; systemic vascular resistance; mean pulmonary arterial pressure; and pulmonary vascular resistance. In addition, arterial blood samples for gas and acid-base analyses were collected at 30-minute intervals for 2.5 hours. After baseline values were recorded, dogs were randomly assigned to receive either buprenorphine (16 micrograms/kg, i.v.) or isovolumetric 5% dextrose solution. All variables were then recorded at 15-minute intervals for 2.5 hours.. During isoflurane anesthesia, buprenorphine administration caused significant (P < or = 0.05) reductions in diastolic arterial pressure, mean arterial pressure, systolic arterial pressure, cardiac index, and heart rate, whereas systemic vascular resistance increased significantly. During halothane anesthesia, buprenorphine administration caused significant decreases in heart rate, cardiac index, mean, systolic and diastolic arterial blood pressures, and stroke volume, whereas pulmonary arterial blood pressure and systemic vascular resistance increased significantly.. Although the changes seen were significant, they were not sufficiently large to be of clinical importance in healthy dogs.

Topics: Analgesics, Opioid; Anesthesia, Inhalation; Anesthetics, Inhalation; Animals; Blood Pressure; Body Weight; Buprenorphine; Cardiac Output; Cardiovascular Physiological Phenomena; Dogs; Drug Interactions; Female; Halothane; Heart Rate; Isoflurane; Male; Stroke Volume; Vascular Resistance

To characterize the hemodynamic effects of medetomidine (1 mg/m2 of body surface area; dosage, 39 to 46 micrograms/kg of body weight, IM) and midazolam (1 mg/kg of body weight, i.v.) combined with butorphanol (0.1 mg/kg, i.v.), buprenorphine (10 micrograms/kg, i.v.) or saline solution. Reversibility of these effects by atipamezole (2.5 mg/m2; dosage, 97.5 to 115 micrograms/kg, IM) was evaluated.. 2 treated groups and 1 control group, without repetition.. 15 clinically normal dogs (3 groups of 5).. Medetomidine was administered at time 0; midazolam and butorphanol, buprenorphine, or saline solution at time 20; and atipamezole at time 60. Heart rate, systemic and pulmonary arterial pressures, central venous pressure, body temperature, cardiac output, and arterial and mixed venous blood gas tensions and pH were measured. Cardiac index, stroke index, systemic and pulmonary vascular resistances, and left and right stroke work indexes were calculated.. Body temperature, heart rate, cardiac index, and stroke index were significantly decrease below baseline values in some groups. Central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance were significantly increased above baseline in all groups. Arterial and venous PO2 and pH decreased in all groups and PCO2 increased, but these changes were more pronounced when buprenorphine was administered. Arterial pressure decreased after atipamezole administration.. The combinations seemed to result in cardiorespiratory depressant effects of similar importance and most of these effects, which are related to medetomidine, were reversed by atipamezole.

Topics: Adrenergic alpha-Antagonists; Analgesics; Animals; Anti-Anxiety Agents; Blood Gas Analysis; Blood Pressure; Body Temperature; Body Weight; Buprenorphine; Butorphanol; Cardiac Output; Dogs; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Heart Rate; Hemodynamics; Hydrogen-Ion Concentration; Imidazoles; Medetomidine; Midazolam; Pulmonary Wedge Pressure; Stroke Volume; Vascular Resistance

In order to use buprenorphine as an analgesic in immunological experiments, we have studied the potential immunotoxicity of buprenorphine. Three-week-old male Wistar Riv:TOX rats were subcutaneously treated with buprenorphine by injection of 0.1, 0.4, or 1.6 mg/kg body weight per day over a period of 4 weeks. Concentrations used were within the range for analgesia in rats. A slight decrease of body weight gain was observed at the highest dose in one but not in a duplicate study. Decreased liver weights were observed in all dose groups. Histopathologically glycogen storage was decreased and fatty vacuolation was found to be increased starting from the lowest dose group. The relative but not absolute weight of the lungs was slightly increased at the lowest dose, this phenomenon was therefore not dose-dependent. Histopathologically, a dose-dependent increase in interstitial pneumonia in the lung was found. At the 2 higher dose levels the weight of the adrenal glands was increased. No haematological changes were found, nor were there effects on bone marrow. In one of 2 studies indications of potential immunotoxicity noted were: an increased weight of the thymus, as well as an increased weight of popliteal and mesenteric lymph nodes. No effects on the weight of the spleen were found. Histologically, there were no changes in the lymphoid organs tested. Total immunoglobulin A concentrations in serum were significantly decreased in the highest dose group, whereas IgG concentrations were increased, albeit not statistically significantly. IgM and IgE concentrations showed no alterations. Two types of immune function assays were carried out: determination of natural killer cell activity and of mitogen responsiveness of spleen cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analysis of Variance; Animals; Blood Cell Count; Body Weight; Bone Marrow; Bone Marrow Cells; Buprenorphine; Immunoglobulin Isotypes; Killer Cells, Natural; Lymphocyte Activation; Lymphoid Tissue; Male; Organ Size; Rats; Rats, Wistar

Rats underwent a midline laparotomy and received buprenorphine, buprenorphine together with carprofen, flunixin or carprofen alone while a control group received saline. Food and water intakes and body weight were reduced following surgery in the saline control group. The degree of depression of these variables was significantly reduced by the administration of either buprenorphine or carprofen. In all groups of rats locomotor activity was depressed following surgery. Analgesic administration had little influence on these changes in activity, although administration of two doses of buprenorphine (0.05 mg/kg, 9 h interval) reduced the degree of depression in comparison to the saline control group. If the depression in food and water consumption is related to the presence of post-operative pain, then these findings suggest that analgesics should be administered to rats following surgical procedures.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Buprenorphine; Carbazoles; Clonixin; Drinking; Drug Therapy, Combination; Eating; Laparotomy; Male; Motor Activity; Pain, Postoperative; Rats; Rats, Wistar

The post-operative effects of laparotomy and common bile-duct ligation were investigated in rats. Bile-duct ligation caused a significant reduction in food and water consumption, body weight and locomotor activity in the immediate post-operative period. Animals which underwent laparotomy in which bile-duct ligation was not carried out (sham operated groups) had significantly less depression of food and water consumption and body weight than groups which underwent bile-duct ligation. The detrimental effects on food and water consumption and body weight could be significantly reduced by the administration of buprenorphine (0.05 mg/kg, s/c), but not by infiltration of the surgical wound with the long-acting local anaesthetic agent, bupivacaine. The reduction of the depressant effects of surgery on food and water consumption by the opioid analgesic buprenorphine suggests that some of these changes may be related to the presence of post-operative pain.

Topics: Animals; Bile Ducts; Body Weight; Bupivacaine; Buprenorphine; Laparotomy; Ligation; Male; Pain, Postoperative; Postoperative Period; Rats; Rats, Wistar

This study assessed the relationship between autotomy and opioid systems following brachial nerve sections in the rat. Morphine, buprenorphine and/or naloxone were self-administered orally to rats following nerve sections. Oral morphine and buprenorphine increased the severity of autotomy. Naloxone alone had no effect, but reversed oral morphine effect on autotomy. These results suggest that mu-receptor activation by morphine and buprenorphine can increase the severity of autotomy.

Topics: Administration, Oral; Animals; Body Weight; Brachial Plexus; Buprenorphine; Denervation; Dose-Response Relationship, Drug; Drug Administration Schedule; Male; Morphine; Naloxone; Pain; Rats; Rats, Inbred F344; Self Mutilation

In physical dependence studies in rats the principle criterion was loss of body weight after withdrawal of the dependence producing drug. Other typical signs of withdrawal were also observed. In contrast to buprenorphine, codeine and tramadol, flupirtine caused no decrease in body weight and no other withdrawal symptoms. Flupirtine does not produce opiate type physical dependence.

Topics: Aminopyridines; Analgesics; Animals; Body Weight; Buprenorphine; Codeine; Female; Rats; Rats, Inbred Strains; Receptors, Opioid; Substance-Related Disorders; Tramadol

Topics: Animals; Behavior, Animal; Body Weight; Buprenorphine; Dose-Response Relationship, Drug; Macaca mulatta; Male; Morphinans; Morphine; Reinforcement, Psychology