Peripheral kappa-opioid modulation of the formalin response: an electrophysiological study in the rat.
The activity of single dorsal horn nociceptive neurones was recorded in the spinal cord of halothane anaesthetized rats. S.c. injection of a 5% formalin solution into the receptive field of these neurones resulted in two peaks of neuronal firing over a period of 60 min. Prior administration of the kappa-opioid receptor agonist U50488H directly into the site of formalin injection caused a dose-dependent decrease in the size of both the first and second peaks of the response which was naloxone reversible. Injection of U50488H into the contralateral paw had no effect on either peak of the formalin response. Injection of the top dose (100 micrograms) of U50488H had no effect on the electrically evoked A beta- or C-fibre responses of the neurone. Neither morphine nor Tyr-D-Ser(Otbu)-Gly-Phe-Leu-Thr (DSTBULET), administered into the receptive field, had any significant effect on either peak of the formalin response. Plasma extravasation in the skin, measured using Evans blue, produced by the formalin injection was not blocked by U50488H. Thus, whilst the spinal responses of this peripheral model of inflammation can be inhibited by peripheral kappa-opioid activation, but not mu- or delta-, plasma extravasation associated with this inflammation is not reduced.
Haley
J
J
Department of Pharmacology, University College London, U.K.
Ketchum
S
S
Dickenson
A
A
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D005070:Evans Blue; D005557:Formaldehyde / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa
D000700:Analgesics; D009842:Oligopeptides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C054868:tyrosyl-seryl(O-tert-butyl)-glycyl-phenylalanyl-leucyl-threonine; D005557:Formaldehyde; D009270:Naloxone; D005070:Evans Blue; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer