| First Author | Devesa I | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 51 | Pages | 18345-50 |
| PubMed ID | 25489075 | Mgi Jnum | J:216942 |
| Mgi Id | MGI:5610062 | Doi | 10.1073/pnas.1420252111 |
| Citation | Devesa I, et al. (2014) alphaCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors. Proc Natl Acad Sci U S A 111(51):18345-50 |
| abstractText | Proalgesic sensitization of peripheral nociceptors in painful syndromes is a complex molecular process poorly understood that involves mobilization of thermosensory receptors to the neuronal surface. However, whether recruitment of vesicular thermoTRP channels is a general mechanism underlying sensitization of all nociceptor types or is subtype-specific remains controversial. We report that sensitization-induced Ca(2+)-dependent exocytotic insertion of transient receptor potential vanilloid 1 (TRPV1) receptors to the neuronal plasma membrane is a mechanism specifically used by peptidergic nociceptors to potentiate their excitability. Notably, we found that TRPV1 is present in large dense-core vesicles (LDCVs) that were mobilized to the neuronal surface in response to a sensitizing insult. Deletion or silencing of calcitonin-gene-related peptide alpha (alphaCGRP) gene expression drastically reduced proalgesic TRPV1 potentiation in peptidergic nociceptors by abrogating its Ca(2+)-dependent exocytotic recruitment. These findings uncover a context-dependent molecular mechanism of TRPV1 algesic sensitization and a previously unrecognized role of alphaCGRP in LDCV mobilization in peptidergic nociceptors. Furthermore, these results imply that concurrent secretion of neuropeptides and channels in peptidergic C-type nociceptors facilitates a rapid modulation of pain signaling. |
