title: Spinal TRPA1 ion channels contribute to cutaneous neurogenic inflammation in the rat.
abstract: In the spinal dorsal horn, TRPA1 ion channels on central terminals of peptidergic primary afferent nerve fibers regulate transmission to glutamatergic and GABAergic interneurons. Here we determine the cutaneous anti-inflammatory effect of a spinally administered TRPA1 channel antagonist to test the hypothesis that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation induced by sustained noxious stimulation. According to the hypothesis, spinal TRPA1 channels facilitate transmission of injury discharge to GABAergic interneurons that induce a dorsal root reflex, which results in increased release of proinflammatory compounds in the skin. Intraplantar capsaicin, a TRPV1 channel agonist, was used to induce neurogenic inflammation in anesthetized rats that were pretreated intrathecally (i.t.), intraplantarly (i.pl.) or intraperitoneally (i.p.) with vehicle or Chembridge-5861526 (CHEM, a TRPA1 channel antagonist). For assessment of neurogenic inflammation, the capsaicin-induced increase of cutaneous blood flow was determined adjacent to the capsaicin-treated skin site with a laser Doppler flowmeter. Capsaicin-induced a marked increase in cutaneous blood flow. The capsaicin-induced blood flow increase was attenuated in a dose-related fashion by i.t. pretreatment with CHEM (3-10microg). Pretreatment with CHEM at a dose of 3mg/kg i.p. or 20microg i.pl. failed to attenuate the capsaicin-induced increase of blood flow. The results indicate that spinal TRPA1 channels contribute to cutaneous neurogenic inflammation adjacent to the injury site, probably by facilitating a dorsal root reflex in peptidergic primary afferent nerve fibers.
authors.affiliation: Institute of Biomedicine/Physiology, Biomedicum Helsinki, P.O.B. 63, FIN-00014, University of Helsinki, Helsinki, Finland.
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.forename: Ari
authors.initials: A
authors.lastname: Koivisto
authors.forename: Antti
authors.initials: A
authors.lastname: Pertovaara
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D003872:Dermatitis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D020078:Neurogenic Inflammation / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D012018:Reflex; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000503:physiopathology; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels
chemical_list: D017487:Ankyrins; D015220:Calcium Channels; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat