{"doi":"10.1186/1744-8069-3-30","title":"Roles of TRPV<sub>1</sub>and Neuropeptidergic Receptors in Dorsal Root Reflex-Mediated Neurogenic Inflammation Induced by Intradermal Injection of Capsaicin","abstract":"<jats:sec><jats:title>Background:</jats:title><jats:p>Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-1 (TRPV<jats:sub>1</jats:sub>) receptors following intradermal injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs). Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV<jats:sub>1</jats:sub>receptors initiates neurogenic inflammation via triggering DRRs.</jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p>Here we used pharmacological manipulations to analyze the roles of TRPV<jats:sub>1</jats:sub>and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by intradermal injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin injection was assessed by measurements of local blood flow (vasodilation) and paw-thickness (edema) of the foot skin in anesthetized rats. Local injection of capsaicin, calcitonin gene-related peptide (CGRP) or substance P (SP) resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABA<jats:sub>A</jats:sub>receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV<jats:sub>1</jats:sub>receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30–150 μg. In contrast, pretreatment of the periphery with different doses of CGRP<jats:sub>8–37</jats:sub>(a CGRP receptor antagonist) or spantide I (a neurokinin 1 receptor antagonist) only reduced the inflammation. If both CGRP and NK<jats:sub>1</jats:sub>receptors were blocked by co-administration of CGRP<jats:sub>8–37</jats:sub>and spantide I, a stronger reduction in the capsaicin-initiated inflammation was produced.</jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p>Our data suggest that 1) the generation of DRRs is critical for driving the release of neuropeptides antidromically from primary afferent nociceptors; 2) activation of TRPV<jats:sub>1</jats:sub>receptors in primary afferent nociceptors following intradermal capsaicin injection initiates this process; 3) the released CGRP and SP participate in neurogenic inflammation.</jats:p></jats:sec>","journal":"Molecular 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