反復寒冷ストレス負荷ラットにおけるノイロトロピンの鎮痛効果：モノアミン作動性下行性疼痛抑制系神経の化学的除神経の影響

抄録

　Neurotropin^® (NTP), a non protein extract from inflamed rabbit skin inoculated with vaccinia virus, is well known as an analgesic for chronic pain such as low back pain and postherpetic pain. In previous study, we revealed that NTP activated monoaminergic descending pain inhibitory system in SART (specific alternation of rhythm in temperature) stressed animals. To clarify the details of antinociceptive mechanisms of NTP, we investigated the influence of chemical denervation of monoaminergic neurons on the antinociceptive effect of NTP in SART-stressed rats. First, serotonergic neurons of nucleus raphe magnus (NRM) were chemically denervated by injection of 5,7-dihydroxytryptamine (50 nmol / 1 µL / site). Chemical denervation of NRM serotonergic neurons decreased the contents of spinal serotonin but not noradrenaline and dopamine, and decreased nociceptive threshold in rats. SART stress decreased nociceptive threshold in non-denervated rats but not in denervated rats whose threshold was already decreased. NTP (200 NU/kg, p.o.) showed an antinociceptive effect in non-denervated rats exposed to SART stress but had no effect in NRM-denervated rats exposed to SART stress. Next, we denervated spinal noradrenergic terminals by intrathecal injection of 6-hydroxydopamine (1 µmol / 10 µL / site) because some noradrenergic neurons are descending from some supraspinal noradrenergic nucleus to spinal cord. Chemical denervation of spinal noradrenergic neurons decreased the contents of spinal nor adrenaline but not serotonin and dopamine in rats. Similar to denervation of NRM serotonergic neurons, nociceptive threshold was decreased by chemical denervation of spinal noradrenergic neurons. SART stress decreased the nociceptive threshold in non-denervated rats, and that was improved by NTP (200 NU/kg, p.o.). SART stress did not affect the decreased threshold in denervated rats and NTP (200 NU/kg, p.o.) had no effect in denervated rats exposed to SART stress. These results suggest that antinociceptive effects of NTP in SART-stressed rats involve the activation of monoaminergic descending inhibitory neurons.