Differential effects of the 5HT(1B/1D) receptor agonist naratriptan on trigeminal versus spinal nociceptive responses

In vivo electrophysiological assays in anesthetized rats have been used to compare the effects of the 5HT(1B/1D) receptor agonist, naratriptan, on cen tral trigeminal nociceptive processing from dural and cutaneous inputs with its effects on nociceptive processing in the spinal cord. Naratriptan inhi bited responses of single trigeminal neurons, to noxious electrical and mec hanical stimulation of the dura and face, dose dependently by a maximum of 67+/-3% and 70+/-18% respectively, at 3 mg kg(-1) i.v. In contrast, naratri ptan did not affect spinal dorsal horn neuronal responses to noxious mechan ical stimulation of the hind-paw. These findings suggest that 5HT(1B/1D) re ceptors have differential effects on nociceptive processing in the trigemin al versus spinal dorsal hems and provide a potential explanation for the la ck of general analgesic effects of brain penetrant 5HT(1B/1D) agonist antim igraine drugs.