Women are more likely than men to develop chronic pain conditions but is not clear why this is the case. Here, Sim et al. report that monocytes promote the resolution of inflammatory pain by producing IL-10 that acts directly on sensory neurons. They show increased numbers of IL-10-expressing monocytes in the inflamed skin of male mice compared with females and suggest that this is associated with faster pain resolution in males.
Previously, the authors had reported that IL-10 receptor 1 (1L-10R1) signalling in peripheral sensory neurons alleviates pain by reducing neuronal excitability and upregulating the expression of analgesic proteins. Examining the skin, they found that sensory nerves innervating the epidermis express IL-10R1. They generated transgenic mice that lack IL-10R1 in a population of peripheral sensory neurons and showed that these mice experienced prolonged pain in response to CFA treatment. Therefore, increased IL-10R1 signalling in sensory neurons in the skin of male mice likely contributes to their reduced pain after CFA injection.