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.