Bradykinin Induces TRPV1 Exocytotic Recruitment in Peptidergic Nociceptors

摘要: Transient receptor potential vanilloid I (TRPV1) sensitization in peripheral nociceptors is a prominent phenomenon that occurs inflammatory pain conditions. Pro-algesic agents can potentiate TRPV1 activity through both stimulation of its channel gating and mobilization channels to the neuronal surface context dependent manner. A recent study reported ATP-induced peptidergic involves exocytotic release trafficked by large dense core vesicles (LDCVs) cargo alpha-calcitonin gene related peptide alpha (αCGRP). We hypothesized that, similar ATP, bradykinin may also use different mechanisms sensitize non-peptidergic nociceptors. found notably enhances excitability nociceptors, sensitizes TRPV1, primarily 2 pathway. Notably, was significantly blocked inhibiting Ca2+-dependent exocytosis. In addition, silencing αCGRP expression, but not substance P, drastically reduced bradykinin-induced Taken together, these findings indicate partially mediated new αCGRP-loaded LDCVs membrane. Our further imply central role algesic sensitization, substantiate inhibition exocytosis valuable therapeutic strategy treat pain, as it concurrently reduces pro-inflammatory peptides membrane recruitment thermoTRP channels.