title: The analgesic drug buprenorphine inhibits osteoclastic bone resorption in vitro, but is proinflammatory in rat adjuvant arthritis.
abstract: We have examined the effect of the micro-opioid analgesic buprenorphine on osteoclastic bone resorption in vitro and in the rat adjuvant arthritis model. In the bone slice assay buprenorphine inhibited osteoclastic bone resorption with an IC50 of 1 microM. This effect was not mimicked by the micro-opioid agonist ([D-Ala, N-Me-Phe, Gly-ol]-enkephalin and was not prevented by the micro-opioid antagonist naloxone. Since other agents that inhibit osteoclastic bone resorption, such as bisphosphonates and calcitonin prevent bone erosion in the rat adjuvant arthritis model, we also examined the effect of buprenorphine in this model. Surprisingly, buprenorphine exacerbated inflammation measured by paw volume and increased joint destruction assessed by X-ray scores, in the injected paws and particularly in the non-injected paws. These studies also show that attempts to ameliorate animal suffering in this chronic model by using centrally acting analgesics such as buprenorphine may lead to complications in interpreting screening results obtained with novel, potential anti-arthritic compounds.
authors.affiliation: Ciba-Geigy Ltd., Research Department, Basel, Switzerland.
authors.forename: T J
authors.initials: TJ
authors.lastname: Hall
authors.forename: B
authors.initials: B
authors.lastname: Jagher
authors.forename: M
authors.initials: M
authors.lastname: Schaeublin
authors.forename: I
authors.initials: I
authors.lastname: Wiesenberg
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000000981:diagnostic imaging; D001175:Arthrography; D001862:Bone Resorption / Q000188:drug therapy*; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D005269:Femur / Q000166:cytology / Q000187:drug effects; D007928:Lethal Dose 50; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004745:Enkephalins; D009292:Narcotic Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D002047:Buprenorphine