Evaluation of buprenorphine in a postoperative pain model in rats (original) (raw)
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Laboratory Animals, 2002
Buprenorphine has been widely used for post-operative analgesia in laboratory animals. Clinical efficacy has been demonstrated in both subjective and objective pain assessment schemes, however doubts have been expressed as to its value as an analgesic. Initial dosage recommendations were based on analgesiometric studies. It is unlikely, however, that the pain elicited in analgesiometric tests is comparable to post-operative pain. This has resulted in recommendations of excessive dose rates and inappropriate clinical indications. Studies involving tests of the efficacy of buprenorphine for alleviating behavioural or other signs of tonic (post-surgical) pain provide a more appropriate estimation of the analgesic capabilities of the drug. However, buprenorphine also has major effects upon the behaviour of normal (unoperated) animals, and this makes assessments of efficacy difficult with some of the systems used for scoring clinical pain. Nevertheless, our most recent studies of the eff...
PubMed, 2016
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.
International Journal of Advances in Medicine, 2016
Background: Surgical trauma is a real and severe tissue damage resulting in surgical pain which is a universal phenomenon. Post-surgical pain experienced by patient is often significantly greater than anticipated by the patient. Recognition that inadequate analgesics adversely affect the patient's cardiovascular, pulmonary and emotional status has spurred development of new and highly effective methods of controlling pain. The benefits of postoperative analgesia are speedy recovery, reduction in physical and mental stress, improvement in pulmonary function (by allowing the patient to cough, breath and move more easily), less stress on cardiac function, decreased incidence of thromboembolic complications. Buprenorphine is a highly lipid soluble narcotic of antagonist agonist type which is 40-50 times more potent than morphine. As per available previous researches, low dose of intrathecal buprenorphine produces prolonged postoperative analgesia with lesser side effects. Methods: The present study was carried out in the department of anaesthesiology, CCM medical college, Durg, Chhattisgarh, India during study period August 2015 to July 2016. The study comprised of 80 patients undergoing surgery of lower abdomen below umbilicus (T10) and lower limbs. Patients of age Group between 20-60 years of age of either sex of ASA group I and II were included in the study. Pre-anesthetic evaluation was done prior to surgery. The patients were randomly divided into 2 groups [group-I (control), group II (Buprenorphine hydrochloride 0.06 mg intrathecally)] of 40 patients each. All the patients were informed about visual analogue scale preoperatively. After the surgical process, observations were recorded. The assessment of results of both groups were done. The results were analysed by unpaired' test and p value. Results: Mean age in both the groups were comparable and statistically insignificant (p>0.05). Mean age in group I was 39.3±1.5 years and group II was 38.5±12.2. In group II, there was male predominance i.e. M: F was 3: 2, whereas in group I sex ratio was equal (M: F was1:1). Mean weight in both groups were comparable and statistically insignificant (p>0.05). In group I mean weight was 49.5±2.5 kg and 45% pts. Were between 40-50 kg weights. In Group II mean weight was 50.9±8.2 kg and 40% patients were between 40-50 kg weights. Patients receiving study drug has significantly rapid onset of sensory block as compared to control Group (p<0.05). Patients of group II had significantly rapid onset of motor block (p<0.05). The mean duration of surgery in group I was 90.8±44.0, and group II 115.0±40.0 min. The mean duration of motor block in Group I was 190.5±57.2 min and group II was 186.5±30.1 min (3.12+ 0.52 hours). Duration of absolute and effective analgesia is significantly higher in Group II. VAS score is significantly lower in group II patients. There was no statistically significant change in systolic blood pressure, diastolic blood pressure and pulse rate attributable to intrathecal buprenorphine. Conclusions: On the basis of observation and results of our study we conclude that buprenorphine has been found to be superior for postoperative analgesia as compared to control group.
Laboratory Animals, 2012
Buprenorphine is commonly used as ( part of ) postoperative analgesic treatment with dosage dependent side-effects such as pica behaviour. No strict consensus exists about the optimal dosing interval of buprenorphine, as its duration of action has been described as being in the range of 6-12 hours. In this study, dosing intervals of eight (thrice-a-day) and 12 (twice-a-day) hours for buprenorphine in a multimodal analgesic strategy (concurrent administration of a non-steroidal anti-inflammatory drug) were compared on food intake, weight and side-effects (gnawing on plastic Petri dishes and growth rate, indicative of pica behaviour) in rats. The food intake and weight of both intervals was comparable, as the animals from the twice-a-day group did not lose more weight or consumed less food during the analgesic period. The rats from the thrice-a-day group suffered from more side-effects, as the growth rate was decreased and more plastic was gnawed on. It is recommended to carefully evaluate analgesic and side-effects when using buprenorphine. When side-effects are observed, the possibility of increasing the dosing interval of buprenorphine should be explored. In this study, increasing the dosing interval of buprenorphine in a multimodal analgesic regimen resulted in reduced unwanted side-effects, without increasing weight loss or decreasing food intake. Although this is suggestive of provision of comparable analgesia, future studies including more pain-related readout parameters to assess the effect of the dosing interval on analgesic efficacy are recommended.
Journal of the American Association for Laboratory Animal Science : JAALAS, 2011
Postoperative pain management in laboratory animals relies heavily on a limited number of drug classes, such as opioids and nonsteroidal antiinflammatory drugs. Here we evaluated the effects of saline, tramadol, tramadol with gabapentin, and buprenorphine (n = 6 per group) in a rat model of incisional pain by examining thermal hyperalgesia and weight-bearing daily for 6 d after surgery. All drugs were administered preemptively and continued for 2 consecutive days after surgery. Rats treated with saline or with tramadol only showed thermal hyperalgesia on days 1 through 4 and 1 through 3 after surgery, respectively. In contrast, buprenorphine-treated rats showed no thermal hyperalgesia on days 1 and 2 after surgery, and rats given tramadol with gabapentin showed reduced thermal hyperalgesia on days 2 and 4. For tests of weight-bearing, rats treated with saline or with tramadol only showed significantly less ipsilateral weight-bearing on day 1 after surgery, whereas rats given either ...
Molecular, Anatomical, Physiological and Behavioral studies of rats treated with Buprenorphine
Journal of Neurotrauma, 2009
Acute pain is a common symptom experienced after spinal cord injury (SCI). The presence of this pain calls for treatment with analgesics, such as buprenorphine. However, there are concerns that the drug may exert other effects besides alleviation of pain. Among those reported are in vitro changes in gene expression, apoptosis, and necrosis. In this investigation, the effect of buprenorphine was assessed at the molecular, behavioral, electrophysiological, and histological levels after SCI. Rats were injured at the T10 thoracic level using the NYU impactor device. Half of the animals received buprenorphine (0.05 mg=kg) for 3 consecutive days immediately after SCI, and the other half were untreated. Microarray analysis (n ¼ 5) was performed and analyzed using the Array Assist software. The genes under study were grouped in four categories according to function: regeneration, apoptosis, second messengers, and nociceptive related genes. Microarray analysis demonstrated no significant difference in gene expression between rats treated with buprenorphine and the control group at 2 and 4 days post-injury (DPI). Experiments performed to determine the effect of buprenorphine at the electrophysiological (tcMMEP), behavioral (BBB, grid walking and beam crossing), and histological (luxol staining) levels revealed no significant difference at 7 and 14 DPI in the return of nerve conduction, functional recovery, or white matter sparing between control and experimental groups ( p > 0.05, n ¼ 6). These results show that buprenorphine (0.05 mg=kg) can be used as part of the postoperative care to reduce pain after SCI without affecting behavioral, physiological, or anatomical parameters.
Contemporary topics in laboratory animal science / American Association for Laboratory Animal Science, 2000
This study was designed to determine the magnitude and duration of the analgesic effect of three commonly used opioids: buprenorphine (0.5 mg/kg for rats; 2.0 mg/kg for mice), butorphanol (2.0 mg/kg for rats; 5.0 mg/kg for mice), and morphine (10 mg/kg for rats and mice). We used two standard tests, the hot plate and tail flick assays, to measure opioid analgesia in 62 male, 200 to 300 g Sprague-Dawley rats and 61 male, 25 to 35 g ICR mice. We obtained five baseline measurements then administered the drugs subcutaneously. Morphine gave the highest analgesic effect and was intermediate in duration (2 to 3 h in rats and mice) of analgesia. Butorphanol provided the lowest level of and shortest (1 to 2 h in rats and mice) analgesia. Buprenorphine had an intermediate analgesic effect and the longest duration (6 to 8 h in rats and 3 to 5 h in mice). In light of our results, we recommend the use of morphine (with frequent redosing) for severe pain, butorphanol for mild pain of short durati...
Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats
PLOS ONE, 2016
Concerns over interactions between analgesics and experimental outcomes are a major reason for withholding opioids from rats undergoing surgical procedures. Only a fraction of morphine injected intravenously reaches receptors responsible for analgesia in the central nervous system. Intrathecal administration of morphine may represent a way to provide rats with analgesia while minimizing the amount of morphine injected. This study aimed to assess whether morphine injected intrathecally via direct lumbar puncture provides sufficient analgesia to rats exposed to acute surgical pain (caudal laparotomy).In an initial blinded, randomised study, pain-free rats received morphine subcutaneously (MSC, 3mg. kg-1, N = 6), intrathecally (MIT, 0.2mg.kg-1, N = 6); NaCl subcutaneously (NSC, N = 6) or intrathecally (NIT, N = 6). Previously validated pain behaviours, activity and Rat Grimace Scale (RGS) scores were recorded at baseline, 1, 2, 4 and 8h post-injection. Morphinetreated rats had similar behaviours to NaCl rats, but their RGS scores were significantly different over time and between treatments. In a second blinded study, rats (N = 28) were randomly allocated to one of the following four treatments (N = 7): MSC, 3mg.kg-1, surgery; MIT, 0.2mg.kg-1, surgery; NIT, surgery; NSC, sham surgery. Composite Pain Behaviours (CPB) and RGS were recorded as previously. CPB in MIT and MSC groups were not significantly different to NSC group. MSC and MIT rats displayed significantly lower RGS scores than NIT rats at 1 and 8h postoperatively. RGS scores for MIT and MSC rats were not significantly different at 1, 2, and 8h postoperatively. Intraclass correlation value amongst operators involved in RGS scoring (N = 9) was 0.913 for total RGS score. Intrathecal morphine was mostly indistinguishable from its subcutaneous counterpart, providing pain relief lasting up to 8 hours in a rat model of surgical pain. Further studies are warranted to clarify the relevance of the rat grimace scale for assessing pain in rats that have received opioid analgesics.
Journal of Pain Research, 2013
Purpose: Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain. It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than µ-opioid receptor agonists. The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers. The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia, antihyperalgesia, and descending pain modulation. Subjects and methods: Twenty-eight healthy subjects were included. The study was a doubleblind, randomized, placebo-controlled, five-arm crossover study with a multimodal (electrical, mechanical, and thermal stimuli) testing technique. After baseline assessments, intravenous infusions of morphine (10/20 mg), buprenorphine (0.3/0.6 mg), or placebo (normal saline) were administered over a 210-minute period, during which a cold pressor test, heat injury (47°C, 7 minutes, 12.5 cm 2 ), and the first postburn assessment were done. After completion of the drug infusions, two additional postburn assessments were done. The subjects were monitored during each 8-hour session by an anesthesiologist.