Authors: Okajima, Kenji; Harada, Naoaki

Source: Current Medicinal Chemistry, Volume 13, Number 19, August 2006 , pp. 2241-2251(11)

Publisher: Bentham Science Publishers

Abstract:

Capsaicin-sensitive sensory neurons are nociceptive neurons that release calcitonin gene-related peptide (CGRP) on activation. Since CGRP has potent vasodilatory activity, it has long been considered to be involved in aggravation of inflammation such as tissue hyperemia and edema. However, since ablation of the sensory fibers can result in a marked increase in the severity of inflammation and reperfusion-induced tissue inflammatory responses are enhanced in congenital CGRP-knockout mice, the sensory neurons have been shown to play a role in the maintenance of tissue integrity by regulating local inflammatory responses. We demonstrated in rodents that stimulation of sensory neurons reduces hypertension, stress-induced gastric mucosal injury, reperfusion-induced liver injury, and endotoxin-induced shock responses by attenuating inflammatory responses such as increases in both tissue levels of tumor necrosis factor (TNF) and tissue accumulation of neutrophils. Attenuation of inflammatory responses by sensory neuron activation can be explained mainly by CGRP-induced increase in the endothelial production of prostacyclin (PGI2). Since inflammatory responses are critically involved in the development of a wide variety of diseases, pharmacological stimulation of sensory neurons might contribute to treatment of various pathologic conditions. In this review, the authors describe molecular mechanism(s) by which sensory neuron activation inhibits TNF production, thereby attenuating inflammatory responses. Furthermore, the authors discuss some clinically useful therapeutic agents that are capable of activating sensory neurons and raise the possibility that pharmacological stimulation of sensory neurons is the new paradigm for future therapeutic strategies.

Keywords: Sensory neurons; calcitonin-gene related peptide; vanilloid receptor-1; endothelial nitric oxide synthase; prostaglandins; tumor necrosis factor

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986706777935131

Affiliations: 1: Department of Biodefense Medicine, Nagoya City University Graduate School of Medical Sciences,Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.

Publication date: 2006-08-01

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• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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