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Comparison of Buprenorphine and Meloxicam for Postsurgical Analgesia in Rats: Effects on Body Weight, Locomotor Activity, and Hemodynamic Parameters
Authors:Stephane L Bourque   Michael A Adams   Kanji Nakatsu     Andrew Winterborn
Affiliation:1Department of Pharmacology and Toxicology, Queen''s University, Kingston, Ontario, Canada;2Office of the University Veterinarian, Queen''s University, Kingston, Ontario, Canada
Abstract: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.Abbreviation: HR, heart rate; MAP, mean arterial pressure; WD, Western dietIn collaboration with facility veterinarians, researchers who perform invasive surgical techniques must decide on an appropriate postoperative pain management regimen. From an ethical perspective, minimizing an animal''s suffering should be a primary concern. Moreover, inadequate pain management can compromise a study''s outcome, because activation of the pain cascade can influence physiologic function.10 In addition, the full pharmacodynamic spectrum of the analgesic drug should be considered, because any of its activities could affect a study''s endpoints. Therefore, appropriate selection of drugs for management of postoperative pain is not a trivial decision.Implantation of radiotelemetric transducers is an invasive but necessary surgical procedure for direct and chronic measurement of hemodynamic parameters in animals. Although noninvasive techniques for blood pressure assessments are available, direct assessment by implantation of arterial catheters is generally considered to yield far superior data,13 notwithstanding the cost and surgical expertise required. In rats, implantation of transducers involves an abdominal incision of approximately 4 to 5 cm, visceral manipulation, implantation of a small catheter into the abdominal aorta, suturing the transducer to the inner muscular layer, and finally suturing the abdominal incision.Postoperative analgesia for telemetry implantation, like many other surgeries, often consists of opioid analgesics such as buprenorphine,9,11,20 a partial µ-opioid receptor agonist. Buprenorphine treatment has been shown to improve overall indications of pain and surgical stress, including postoperative food and water intake, changes in body weight, and ambient locomotor activity, compared with those of untreated controls.20 Nevertheless, there can be unwanted effects associated with buprenorphine use, including rebound hyperalgesia,23 variability in potency between sexes and strains of rodents,7 and issues with food intake (such as anorexia and pica).6,15 Furthermore, assessment of postoperative pain and recovery are complicated, given that buprenorphine treatment affects growth rate, feeding, and locomotor activity in naive rats;4,15,19 thus, discriminating between behavioral cues caused by pain compared with those due to buprenorphine treatment per se is problematic. Finally, as an opioid analgesic, buprenorphine use is controlled in most jurisdictions, thereby complicating its availability.Alternative therapeutics for treating postoperative pain include nonsteroidal antiinflammatory drugs such as meloxicam.21 Meloxicam acts by inhibiting cyclooxygenases and thus preventing the synthesis of prostaglandin H2, which is a precursor to mediators that elicit pain and inflammation.24 Although meloxicam is a potential alternative treatment for surgery in rats, knowledge of its effects on recovery and cardiovascular parameters after surgery is incomplete. The objective of this study was to compare the postoperative recovery in rats treated with either buprenorphine or meloxicam for management of pain after surgical implantation of telemetric transducers.
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