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IL-23/IL-17A/TRPV1 axis produces mechanical pain via macrophage-sensory neuron crosstalk in female mice.
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 α (ERα) 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.
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Related Subject Headings
- TRPV Cation Channels
- Signal Transduction
- Sex Factors
- Nociceptors
- Nociceptive Pain
- Neurology & Neurosurgery
- Nerve Fibers, Unmyelinated
- Mice, Inbred C57BL
- Mice
- Male
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=1097-4199&client=dukeuniv)
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- TRPV Cation Channels
- Signal Transduction
- Sex Factors
- Nociceptors
- Nociceptive Pain
- Neurology & Neurosurgery
- Nerve Fibers, Unmyelinated
- Mice, Inbred C57BL
- Mice
- Male