Intrathecal etorphine, fentanyl and buprenorphine on spinal nociceptive neurones in the rat.
Single unit recordings were made in the lumbar dorsal horn in the intact anaesthetized rat from convergent, multireceptive neurones. Activity was evoked by A beta and C fibre transcutaneous electrical stimulation of hind paw receptive fields. Three opioids, fentanyl, etorphine and buprenorphine were applied either intrathecally or intravenously and their effects on neuronal responses were examined. Intrathecal fentanyl and etorphine produced clear selective naloxone-reversible inhibitions of C fibre-evoked responses (ED50 = 24 micrograms and 0.6 micrograms respectively). Fentanyl, a mu opioid receptor agonist, was more potent at a given dose when given systemically, but etorphine, a non-selective opioid agonist, was similarly potent by both routes. In contrast to fentanyl and etorphine, intrathecal buprenorphine produced facilitations of C fibre-evoked responses at a low dose (15 micrograms), but inhibited both C and A beta fibre-evoked responses equally at a higher dose (125 micrograms). Inhibitions were found to be irreversible by naloxone. No inhibition of either C or A beta responses occurred following intravenous buprenorphine (10-1070 micrograms). The results are discussed in the light of the relationships between lipophilicity, opioid receptor selectivity and potency for spinally applied opioids.
Dickenson
A H
AH
Department of Pharmacology, University College London, LondonU.K. Oxford Regional Pain Relief Unit, Abingdon Hospital, Abingdon, OxfordU.K.
Sullivan
A F
AF
McQuay
H J
HJ
D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005048:Etorphine / Q000494:pharmacology*; D005283:Fentanyl / Q000494:pharmacology*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008055:Lipids; D009474:Neurons / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D012995:Solubility; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D008055:Lipids; D002047:Buprenorphine; D005048:Etorphine; D005283:Fentanyl