title: The systemic administration of local anaesthetics produces a selective depression of C-afferent fibre evoked activity in the spinal cord.
abstract: An electrophysiological analysis of the antinociceptive effects of systemic lidocaine and its longer acting primary amine congener, tocainide, has been performed in the decerebrate-spinal unanaesthetised rat. Neither of these local anaesthetic drugs when administered systemically in doses of up to 10 mg/kg (lidocaine) or 100 mg/kg (tocainide), produced any evidence of a block in the conduction of action potentials in A beta, A delta or C primary afferents. The local anaesthetics also failed to reduce mustard oil induced neurogenic extravasation, a test of cutaneous C-fibre terminal function. Lidocaine produced a transient (1-2 min) depression in monosynaptic reflexes at doses of greater than or equal to 1 mg/kg while tocainide had no effect on this reflex at any dose up to a 100 mg/kg. Both drugs, however, significantly suppressed the C-fibre evoked polysynaptic reflex generated by stimulating the sural nerve. The tocainide effect was longer lasting with less action on the short latency A beta-evoked reflex than lidocaine. The reflex activity in hamstring flexor alpha-motoneurones evoked by pinching the toes of the ipsilateral hind paw was reduced by both drugs but not abolished. Thermal and noxious chemical evoked reflexes were, however, completely suppressed by the local anaesthetic drugs, again with a longer action from tocainide. These results demonstrate that the systemic administration of drugs which increase the inactivation of sodium channels can produce a selective central block of certain types of afferent evoked activity in the spinal cord. There are resemblances between the selective C-fibre suppressing actions of systemically administered local anaesthetic and the pharmacological actions of narcotic opiates which may represent a similar mechanism for the analgesic action of these quite different classes of drugs.
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003864:Depression, Chemical; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000502:physiology; D013497:Sural Nerve / Q000502:physiology; D016677:Tocainide
chemical_list: D016677:Tocainide; D008012:Lidocaine