title: Spinal local anaesthetic actions on afferent evoked responses and wind-up of nociceptive neurones in the rat spinal cord: combination with morphine produces marked potentiation of antinociception.
abstract: Lignocaine was tested either alone or in combination with a low dose of morphine by intrathecal administration on the C- and A-beta evoked responses of nociceptive neurones in the dorsal horn of the halothane-anaesthetized rat. In addition the effect of prilocaine was compared to lignocaine. The effects of lignocaine on wind-up, a frequency-dependent increase in the responses of the cells produced by repeated C-fibre stimulation was also tested. Lignocaine produced dose-dependent inhibitions of the C-, A-delta and A-beta evoked responses of the cells which became more selective for the noxious evoked responses as the dose increased. The effective doses corresponded well to those used clinically. Wind-up was also decreased by lignocaine. In combination with a low dose of morphine, threshold doses of lignocaine produced a highly marked potentiation of the inhibitions of the C-fibre evoked responses compared to either agent alone. No potentiation of the inhibitions of the A-beta responses was observed. The potentiated inhibitory effects on the C-fibre responses were rapidly reversed by intrathecal naloxone. The finding that spinal local anaesthetic and morphine potentiate markedly to reduce spinal nociception is discussed both in terms of mechanisms of action of the agents and their clinical application.
authors.affiliation: Department of Pharmacology, University College London, London WC1E 6BT UK.
authors.forename: Harriet M
authors.initials: HM
authors.lastname: Fraser
authors.forename: Victoria
authors.initials: V
authors.lastname: Chapman
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D000344:Afferent Pathways / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005071:Evoked Potentials / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; D009270:Naloxone; D009020:Morphine; D008012:Lidocaine