Evaluation of buprenorphine in a postoperative pain model in rats.

Abstract

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.

• Authors: Leslie I Curtin, Julie A Grakowsky, Mauricio Suarez, Alexis C Thompson, Jean M DiPirro, Lisa B E Martin, Mark B Kristal
• Journal: Comparative medicine (Comp Med) Vol. 59 Issue 1 Pg. 60-71 (Feb 2009) ISSN: 1532-0820 [Print] United States
• PMID: 19295055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Buprenorphine
• Morphine

Topics

• Analgesics, Opioid (therapeutic use)
• Animals
• Buprenorphine (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Hyperalgesia (chemically induced, prevention & control)
• Injections, Subcutaneous
• Locomotion (drug effects)
• Male
• Morphine (pharmacology)
• Pain Measurement
• Pain Threshold (drug effects)
• Pain, Postoperative (physiopathology, prevention & control)
• Rats
• Rats, Long-Evans
• Time Factors