bemesetron and Chronic-Disease

Neurotropin((R)), 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 alpha(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.

Topics: Administration, Oral; Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Antagonists; Analgesics; Animals; Arthritis, Experimental; Chronic Disease; Clonidine; Dose-Response Relationship, Drug; Hyperalgesia; Injections, Intravenous; Injections, Spinal; Lumbosacral Region; Male; Methysergide; Pain; Pain Threshold; Polysaccharides; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Adrenergic, alpha-2; Receptors, Serotonin; Serotonin Antagonists; Time Factors; Tropanes; Yohimbine

Intraplantar administration of serotonin 5-HT3 receptor antagonists ICS 205-930 and MDL 72222 (1-100 micrograms; 50 microliters) produced dose-related analgesia against formalin-induced acute- and Freunds adjuvant-induced chronic-inflammatory pain in rats. 5-HT3 receptor antagonists had greater effect in the chronic pain test than in the acute paradigm. In both tests, ICS 205-930 was more potent than MDL 72222. These data further support the involvement of peripheral 5-HT3 sites in inflammatory pain, and suggest the utility of selective 5-HT3 receptor antagonists as peripheral analgesics.

Topics: Acute Disease; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Indoles; Male; Nociceptors; Pain Measurement; Rats; Serotonin Antagonists; Tropanes; Tropisetron