title: The effects of sympathetic outflow on upregulation of vanilloid receptors TRPV(1) in primary afferent neurons evoked by intradermal capsaicin.
abstract: The vanilloid receptor TRPV(1) is a key nociceptive molecule located in primary afferent nociceptive neurons in dorsal root ganglia (DRG) for initiating neurogenic inflammation and pain. Our recent study demonstrates that up-regulation of TRPV(1) receptors by intradermal injection of capsaicin is modulated by activation of the protein kinase C (PKC) cascade. Neurogenic inflammation and pain resulting from capsaicin injection are sympathetically dependent, responding to norepinephrine, adenosine 5'-triphosphate (ATP) and/or neuropeptide Y released from sympathetic efferents. In a rat model of acute neurogenic inflammatory pain produced by capsaicin injection, we used immunofluorescence and Western blots combined with pharmacology and surgical sympathectomies to analyze whether the capsaicin-evoked up-regulation of TRPV(1) in DRG neurons is affected by sympathetic outflow by way of activating the PKC cascade. Sympathetic denervation reduced significantly the capsaicin-evoked expressions of TRPV(1), calcitonin gene-related peptide and/or phosphorylated PKC and their co-expression. These reductions could be restored by exogenous pretreatment with an analog of ATP, alpha,beta-methylene ATP. Inhibition of PKC with chelerythrine chloride prevented the ATP effect. Consistent results were obtained from experiments in which capsaicin-evoked changes in cutaneous inflammation (vasodilation and edema) were examined after sympathetic denervation, and the effects of the above pharmacological manipulations were evaluated. Our findings suggest that the capsaicin-evoked up-regulation of TRPV(1) receptors in DRG neurons is modulated sympathetically by the action of ATP released from sympathetic efferents to activate the PKC cascade. Thus, this study proposes a potential new mechanism of sympathetic modulation of neurogenic inflammation.
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Xijin
authors.initials: X
authors.lastname: Xu
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zou
authors.forename: Dingge
authors.initials: D
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Kerui
authors.initials: K
authors.lastname: Gong
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D004333:Drug Administration Routes; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000166:cytology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008663:Metacarpus / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D018689:Sensory System Agents / Q000494:pharmacology*; D013562:Sympathectomy / Q000379:methods; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin