NEUROTROPIN INDUCES ANTINOCICEPTIVE EFFECT BY ENHANCING DESCENDING PAIN INHIBITORY SYSTEMS INVOLVING 5-HT3 AND NORADRENERGIC ALPHA(2) RECEPTORS IN SPINAL DORSAL HORN

Neurotropin, a non-protein extract from the inflamed skin of rabbits i noculated with vaccinia virus, has been clinically used as an analgesi c drug in Japan. Its analgesic effect has been demonstrated by reduced mechano-nociception in hyperalgesic rats exposed to SART-stress (a re peated cold stress) for 5 days. In order to clarify the mechanism of t he analgesic effect of neurotropin at the spinal cord level, we examin ed the effects of several neurotransmitter receptor antagonists given by intrathecal (i.t.) injection on the antinociceptive effect of intra peritoneally (i.p.) injected neurotropin [100 and 200 Neurotropin Unit (NU)/kg]. The analgesic effect of neurotropin was significantly inhib ited not only by methysergide (100 nmol/rat, i.t.), a non-selective an tagonist against serotonin (5-HT), but also MDL 72222 (30 nmol/rat, i. t.), a selective 5-HT3 antagonist, but not influenced by ketanserin (1 00 nmol/rat, i.t.), a 5-HT2A antagonist. The antinociceptive effect of neurotropin (200 NU/kg, i.p.) was significantly inhibited also by yoh imbine (30 nmol/rat i.t), a noradrenergic alpha(2) antagonist. However , the analgesic effect of neurotropin (100 and 200 NU/kg, i.p.) was no t influenced by naloxone (30 nmol/rat, i.t.), an opioid antagonist. Th ese results suggest that the mechanism of the antinociceptive effect o f neurotropin is via enhancement of endogenous descending pain inhibit ory pathways of the serotonergic and noradrenergic systems, especially involving 5-HT3 and noradrenergic alpha(2) receptors in spinal dorsal horn in which these neurons terminate. No influence of opioid recepto rs at the spinal cord level is indicated.