Inhibitory mechanisms of the hyper-irritability caused by picrotoxin in the rat

Topically applied norepinephrine, dopamine, serotonin, GABA and glycine, and systemically administered clonidine, l-DOPA (plus carbidopa) and 5-hydroxytryptophan completely suppressed the cutaneous hyper-irritability produced in the trigeminal sensory distribution by picrotoxin overlying the caudal medulla. Cholinergic agents and apomorphine were ineffective. Of the positive compounds, norepinephrine, serotonin and GABA showed the shortest latencies and norepinephrine and serotonin required the lowest concentrations in order to inhibit the hyper-irritability. If l-DOPA (plus carbidopa) was injected after pre-treatment with FLA-63, the effects of l-DOPA did not appear. Similar depression of the hyper-irritability was caused by electrical stimulation of the central gray. The inhibitory effects of stimulation of the central gray was suppressed after administration of tetrabenazine, but again produced markedly by injection of l-DOPA. From these observations it was concluded that the hyper-irritability could be suppressed by serotonergic as well as noradrenergic fibers terminating at the spinal trigeminal nucleus caudalis. The potential clinical use of l-DOPA in patients with hyperesthesia is discussed.