title: Regulation of inflammatory responses by sensory neurons: molecular mechanism(s) and possible therapeutic applications.
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 (PGI(2)). 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.
authors.affiliation: Department of Biodefense Medicine, Nagoya City University Graduate School of Medical Sciences, Japan. whynot@med.nagoya-cu.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
authors.forename: Naoaki
authors.initials: N
authors.lastname: Harada
mesh_terms: D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D002211:Capsaicin / Q000627:therapeutic use; D004731:Endotoxins; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D012772:Shock, Septic / Q000188:drug therapy; D050916:TRPV Cation Channels / Q000502:physiology; D014665:Vasodilator Agents
chemical_list: D004731:Endotoxins; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014665:Vasodilator Agents; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin