| First Author | Luo X | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 17 | Pages | 2691-2706.e5 |
| PubMed ID | 34473953 | Mgi Jnum | J:320653 |
| Mgi Id | MGI:6838366 | Doi | 10.1016/j.neuron.2021.06.015 |
| Citation | Luo X, et al. (2021) IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice. Neuron 109(17):2691-2706.e5 |
| abstractText | Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling is not well studied. Here we report that administration of IL-23 produces mechanical pain (mechanical allodynia) in female but not male mice, and chemotherapy-induced mechanical pain is selectively impaired in female mice lacking Il23 or Il23r. IL-23-induced pain is promoted by estrogen but suppressed by androgen, suggesting an involvement of sex hormones. IL-23 requires C-fiber nociceptors and TRPV1 to produce pain but does not directly activate nociceptor neurons. Notably, IL-23 requires IL-17A release from macrophages to evoke mechanical pain in females. Low-dose IL-17A directly activates nociceptors and induces mechanical pain only in females. Finally, deletion of estrogen receptor subunit alpha (ERalpha) in TRPV1(+) nociceptors abolishes IL-23- and IL-17-induced pain in females. These findings demonstrate that the IL-23/IL-17A/TRPV1 axis regulates female-specific mechanical pain via neuro-immune interactions. Our study also reveals sex dimorphism at both immune and neuronal levels. |
