Intrathecal substance P depresses spinal motor and sensory responses to stimulation of nociceptive afferents--antagonism by naloxone.
The effect of an injection of substance P into the subarachnoid space was studied on a motor and a sensory response elicited by supramaximal stimulation of the sural nerve in spinal rats. Substance P 10 micrograms depressed the reflex activation in the electromyogram recorded from the ipsilateral tibialis anterior muscle; the depression was significant 5 and 10 min after the injection. Substance P 10 micrograms reduced the activity in ascending axons of the spinal cord evoked by stimulation of afferent C fibres; the effect developed slowly, lasted longer than 60 min and was abolished by an i.v. injection of nalaoxone 0.2 mg/kg. Only half the number of ascending axons tested showed a depression by substance P, and the administration of a higher dose (50 micrograms) did not produce an effect in a greater number of axons. Substance P did not influence the activity evoked in ascending axons by stimulation of afferent A beta and A delta fibres. The depression by substance P of ascending nocieceptive activity was antagonized by an i.v. injection of naloxone 0.2 mg/kg. When naloxone 0.2 mg/ng i.v. was administered alone, it increased the activity in ascending axons activated by afferent C fibre stimulation. It is concluded that (i) substance P depresses spinal nociceptive activity without the intermediation of endorphinergic neurons, and (ii) naloxone antagonizes tonic inhibition of the spinal nociceptive system mediated by endogenous opioid peptides and, by facilitating excitatory transmission through disinhibition, neutralizes the depression produced by substance P.
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D005260:Female; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D013373:Substance P; D009270:Naloxone