title: The role of spinal opioid receptors in antinociceptive effects produced by intrathecal administration of hydromorphone and buprenorphine in the rat.
abstract: The intrathecal administration of morphine has been the standard therapy to control long-term intractable pain. Recently, a panel of pain therapy experts suggested that because of the lack of efficacy or because of the side effects produced by morphine in some patients, other drugs, such as hydromorphone and buprenorphine, should be investigated for their analgesic properties. We designed this study to compare the efficacy of intrathecal hydromorphone and buprenorphine to suppress thermal nociception in male Sprague-Dawley rats. An additional objective was to understand whether hydromorphone and buprenorphine bind and act as agonists to mu-, delta-, and kappa-spinal opioid receptors. Intrathecally-administered hydromorphone and buprenorphine produced a dose- and time-dependent increase in the tail-flick response latency in rats. The 50% effective dose value for the antinociceptive effect of buprenorphine and hydromorphone were 4 and 69.5 nmol/L, respectively. Both drugs act as agonists to mu-opioid receptors, as determined by their ability to displace [(3)H]-DAMGO from the spinal opioid receptors and by the ability of an opioid receptor antagonist, naloxone, to reverse their antinociceptive effects. Buprenorphine also has an agonistic effect on the kappa-opioid receptors. For the first time, we report that intrathecal buprenorphine is approximately 17 times more effective than hydromorphone in inhibiting thermal pain, and buprenorphine produces its antinociceptive effect by acting as an agonist at both mu- and kappa-spinal opioid receptors. Naloxone administered intrathecally was effective in preventing the antinociceptive effects of subsequent intrathecal injections of buprenorphine.
  
  
  CONCLUSIONS
  Hydromorphone and buprenorphine are two important drugs used for pain relief. We observed that intrathecal buprenorphine is 17 times more potent than hydromorphone to inhibit pain in rats. Both drugs exert their effects through specific spinal opioid receptors.
authors.affiliation: Department of Pharmacology, College of Medicine and Public Health, Ohio State University, 5197 Graves Hall, 333 W 10th Avenue, Columbus, OH 43210-1239, USA. Tejwani.1@osu.edu
authors.forename: Gopi A
authors.initials: GA
authors.lastname: Tejwani
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rattan
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004091:Hydromorphone / Q000008:administration & dosage / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D008024:Ligands; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D004091:Hydromorphone