Mechanisms of analgesic action of neurotropin on chronic pain in adjuvant-induced arthritic rat: roles of descending noradrenergic and serotonergic systems.
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.
Miura
Tomoshi
T
Department of Development Research, Institute of Bio-Active Science, Nippon-Zoki Pharmaceutical Company, Hyogo. t-miura@nippon-zoki.co.jp
Okazaki
Ryohei
R
Yoshida
Hiroyuki
H
Namba
Hiroyoshi
H
Okai
Hisashi
H
Kawamura
Minoru
M
D000284:Administration, Oral; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D002908:Chronic Disease; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000209:etiology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008161:Lumbosacral Region; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014326:Tropanes / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D011134:Polysaccharides; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014326:Tropanes; D015016:Yohimbine; C010491:neurotropin; D003000:Clonidine; C042253:bemesetron; D008784:Methysergide