Exposing mice to 24 and 4°C in alternate 1 hr periods in the day time and maintaining 4°C at night for several days decreases the tail clamp pressure re quired to evoke pain behavior. This model is referred to as SART (specific alterna tion rhythm of temperature) stress. An extract from inflamed skin of rabbits inocu lated with vaccinia virus (neurotropin) clearly normalized the hyperalgesia in this SART stress model. To clarify the mechanism of the hyperalgesia in SART mice and the mode of the antinociceptive action of neurotropin in this model, the influence of systemically administered neurotransmitter related drugs was studied. 1) Neurotropin, 5-hydroxytryptophan and L-dihydroxyphenylalanine significantly normalized the de crease in nociceptive threshold, and muscimol tended to inhibit it in nociceptive threshold in SART stressed mice. 2) Haloperidol, phenoxybenzamine, reserpine, bicu culline, scopolamine, physostigmine and naloxone alone did not influence the nocicep tive threshold in SART stressed mice.3) The antinociceptive effect of neurotropin was significantly attenuated by p-chlorophenylalanine, haloperidol and phenoxybenza mine; and it was completely inhibited by reserpine. 4) Naloxone, bicuculline, scopola mine and physostigmine had no influence on the antinociceptive effect of neurotropin. These results suggest that hypofunction mainly of the monoaminergic systems contrib utes to hyperalgesia in SART stressed mice and that neurotropin produces the anti nociceptive effect by restoring these neural functions.

These results suggest that the antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems, such as the noradrenergic and serotonergic systems, which project from supraspinal sites to the spinal dorsal horn. In addition, activation of inhibitory GABAergic interneurons via 5-HT(3) receptors by serotonin released in the spinal dorsal horn may also be involved in the antiallodynic action of Neurotropin.

Abstract. Neurotropin ® , a non-protein extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been clinically used as an analgesic drug for treatment of chronic pain. In this study, we investigated the analgesic mechanisms of Neurotropin in the adjuvant-induced arthritic rat, a chronic pain model with inflammation. Neurotropin caused dose-dependent inhibition of hyperalgesia in the adjuvant-induced arthritic rat after single intravenous (10 -100 NU / kg) and oral (30 -200 NU / kg) administration. The analgesic effect of Neurotropin (intravenous 100 NU / kg and oral 200 NU/ kg) was significantly inhibited by intrathecal injections of the a 2 -adrenoceptor antagonist yohimbine (30 nmol / animal) and the selective 5-HT 3 serotonin receptor antagonist MDL72222 (30 nmol / animal), and slightly inhibited by the non-selective serotonin receptor antagonist methysergide (100 nmol / animal). The results suggest that the analgesic action of Neurotropin is at least in part due to the enhancement of noradrenergic and serotonergic descending pain inhibitory pathways. Neurotropin may be useful for the clinical management of chronic pain diseases such as a rheumatoid arthritis and osteoarthritis.

No abstract

No abstract