title: Evaluation of postoperative analgesia in a rat model of incisional pain.
abstract: Effective postoperative analgesia is essential for improving patient well-being and decreasing morbidity. Historical recommendations of postoperative analgesics have been based on their effectiveness in attenuating a nociceptive response in animals that have not undergone a surgical procedure, potentially leading to over- or underestimation of postoperative analgesia requirements. This study was designed to evaluate the efficacy of four analgesics in a model of postsurgical pain, which involves surgical incision of the plantar aspect of the hindpaw in halothane-anesthetized rats. The hindpaw was selected as the injury site because it permits quantitative assessment of mechanical sensitivity, which increases as a consequence of tissue damage. As the primary endpoints for postoperative recovery, mechanical sensitivity and weight gain were determined for 5 days. Analgesic regimens included buprenorphine (0.025, 0.05, and 0.1 mg/kg subcutaneously [s.c.]; 1 ml/kg), fentanyl (0.01 and 0.1 mg/kg intraperitoneally [i.p.]; 1 ml/kg), flunixin meglumine (1.1 and 2.5 mg/kg, s.c.; 1 ml/kg) and acetaminophen (100 and 300 mg/kg orally; approximately 3 & 10 ml/kg). Drugs were administered once daily on days 0, 1, and 2 postoperatively. Buprenorphine, fentanyl, and flunixin all significantly decreased mechanical sensitivity, but buprenorphine provided the highest degree of analgesia during the postoperative treatment period. However, rats treated with buprenorphine exhibited heightened mechanical sensitivity once treatment was discontinued on day 2. Moreover, buprenorphine also compromised weight gain as compared to that of vehicle-treated animals. These findings suggest that potent nonsteroidal anti-inflammatory agents, such as flunixin, may be useful alternatives to opioid-based agents for the control of acute postoperative pain associated with a minor surgical procedure and highlight the importance of assessing the risk-benefit ratio when selecting analgesics and dosing regimens.
authors.affiliation: Department of Pharmacology, Merck Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: Laike
authors.initials: L
authors.lastname: St A Stewart
authors.forename: William J
authors.initials: WJ
authors.lastname: Martin
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D000698:Analgesia; D000700:Analgesics; D000818:Animals; D001696:Biomechanical Phenomena; D002047:Buprenorphine / Q000008:administration & dosage; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005283:Fentanyl / Q000008:administration & dosage; D006614:Hindlimb / Q000601:surgery; D007700:Kinetics; D008297:Male; D023421:Models, Animal; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain
chemical_list: D000700:Analgesics; C014557:flunixin; D000082:Acetaminophen; D002047:Buprenorphine; D005283:Fentanyl; D003002:Clonixin