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.

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ABSTRACT-In guinea pigs actively sensitized with ovalbumin, we have observed that nasal hyper reactivity and hypersensitivity to methacholine causes nasal secretion accompanied by an increase in the density of muscarinic acetylcholine receptor (m-ACh•R) following the appearance of nasal symptoms induced by the ovalbumin challenge. Therefore in the present investigation, we studied the relationship between the density of m-ACh•R and nasal hypersecretion in actively sensitized guinea pigs. There was no relationship between the quantity of nasal secretion and serum Ig G1 or Ig E levels. On the other hand, the sensitivity to methacholine and nasal secretion induced by methacholine were significantly re lated to the density of m-ACh•R located on the nasal mucosa. The quantity of nasal secretion induced by allergen was also correlated significantly to the density of m-ACh•R. These results suggest that the nasal hypersecretion observed in the nasal allergic model may be closely associated with an increase in the density of m-ACh•R located on the nasal mucosa. Keywords:Muscarinic receptor, Nasal hypersensitivity, Allergic rhinitis, Nasal provocation, Serum antibody levelNasal allergy is generally a Type I allergic reaction taking place on the surface of basophils and mast cells which are located on the epithelium of the nasal cavity, and Ig E plays a key role in this reaction (1-3). In addition to its immunological mechanism, an imbalance of the autonomic nervous system has also been impli cated as one of the important factors in eliciting nasal allergic symptoms (4). In fact, an increase in density of muscarinic acetylcholine receptor (m-ACh•R) and a de crease in densities of al (a,-R) and /9-adrenergic recep tors (f3•R) were observed in the nasal mucosa of pa tients with nasal allergy (5-7). It is widely known that the nasal mucosa shows not only specific hyperreactivity to allergens but also non-specific hypersensitivity and hyperreactivity to neuromediators (8, 9), to irritants (10) and to physical stimuli (11). Thus, the changes in the expression of autonomic nerve receptors seem to be related to the appearance of hypersensitivity in the na sal mucosa. At present, however, there is little scien tific evidence about the relationship between the changes in the autonomic nerve receptors and the appearance of nasal mucosal hypersensitivity or of nasal allergy.In the present study, the relationship between the nasal hypersecretion and density of m-ACh•R was in vestigated by using guinea pigs actively sensitized with ovalbumin to clarify the influence of impaired function of the parasympathetic nervous system on the appear ance of nasal mucosal hypersensitivity. MATERIALS AND METHODS Experimental animalsMale Hartley guinea pigs (Japan SLC) weighing 400 to 500 g were used. The animals were housed in a temperature-controlled room at 24°C with a 12-hr light cycle (lights on from 08:00 to 20:00), and food and wa ter were given ad libitum. ChemicalsChemicals were purchased from the following com panies: Fluorescein sodium (ur...

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