Evaluation of buprenorphine in a postoperative pain model in rats.
We evaluated the commonly prescribed analgesic buprenorphine in a postoperative pain model in rats, assessing acute postoperative pain relief, rebound hyperalgesia, and the long-term effects of postoperative opioid treatment on subsequent opioid exposure. Rats received surgery (paw incision under isoflurane anesthesia), sham surgery (anesthesia only), or neither and were treated postoperatively with 1 of several doses of subcutaneous buprenorphine. Pain sensitivity to noxious and nonnoxious mechanical stimuli at the site of injury (primary pain) was assessed at 1, 4, 24, and 72 h after surgery. Pain sensitivity at a site distal to the injury (secondary pain) was assessed at 24 and 72 h after surgery. Rats were tested for their sensitivity to the analgesic and locomotor effects of morphine 9 to 10 d after surgery. Buprenorphine at 0.05 mg/kg SC was determined to be the most effective; this dose induced isoalgesia during the acute postoperative period and the longest period of pain relief, and it did not induce long-term changes in opioid sensitivity in 2 functional measures of the opioid system. A lower dose of buprenorphine (0.01 mg/kg SC) did not meet the criterion for isoalgesia, and a higher dose (0.1 mg/kg SC) was less effective in pain relief at later recovery periods and induced a long-lasting opioid tolerance, indicating greater neural adaptations. These results support the use of 0.05 mg/kg SC buprenorphine as the upper dose limit for effective treatment of postoperative pain in rats and suggest that higher doses produce long-term effects on opioid sensitivity.
Curtin
Leslie I
LI
Division of Comparative Medicine and Laboratory Animal Facilities, School of Medicine and Biomedical Sciences, The University at Buffalo, Buffalo, New York, USA.
Grakowsky
Julie A
JA
Suarez
Mauricio
M
Thompson
Alexis C
AC
DiPirro
Jean M
JM
Martin
Lisa B E
LB
Kristal
Mark B
MB
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D002047:Buprenorphine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007279:Injections, Subcutaneous; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
D000701:Analgesics, Opioid; D002047:Buprenorphine; D009020:Morphine