| First Author | Salib AN | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 9051 |
| PubMed ID | 38643253 | Mgi Jnum | J:349469 |
| Mgi Id | MGI:7625023 | Doi | 10.1038/s41598-024-59424-6 |
| Citation | Salib AN, et al. (2024) Interleukin-1alpha links peripheral Ca(V)2.2 channel activation to rapid adaptive increases in heat sensitivity in skin. Sci Rep 14(1):9051 |
| abstractText | Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown. We previously discovered that peripheral voltage-gated Ca(V)2.2 channels in nerve endings in skin are essential for the rapid, transient increase in sensitivity to heat, but not to mechanical stimuli, that accompanies intradermal capsaicin. Here we report that the cytokine interleukin-1alpha (IL-1alpha), an alarmin, is necessary and sufficient to trigger rapid heat and mechanical hypersensitivity in skin. Of 20 cytokines screened, only IL-1alpha was consistently detected in hind paw interstitial fluid in response to intradermal capsaicin and, similar to behavioral sensitivity to heat, IL-1alpha levels were also dependent on peripheral Ca(V)2.2 channel activity. Neutralizing IL-1alpha in skin significantly reduced capsaicin-induced changes in hind paw sensitivity to radiant heat and mechanical stimulation. Intradermal IL-1alpha enhances behavioral responses to stimuli and, in culture, IL-1alpha enhances the responsiveness of Trpv1-expressing sensory neurons. Together, our data suggest that IL-1alpha is the key cytokine that underlies rapid and reversible neuroinflammatory responses in skin. |
