Grant: Project Grant

Tissue injury, such as occurs in surgical incision and infection, results in a well-orchestrated inflammatory response where immune cells are recruited to the injury site where they clear tissue debris and pathogens to help the tissue heal itself. This immune response also warns the host of damage through the sensation of pain: it is increasingly clear that molecular and cellular interactions between the nervous system and immune system play important roles in the development and maintenance of pain, though the exact cells and signals mediating these effects remain unclear. We recently characterized the contribution of circulating immune cells (including neutrophils, monocytes, and T cells) and their secreted products to inflammatory pain outcomes and found that a specific subset of monocytes mediate mechanical (touch) but not thermal (heat) hypersensitivity. Specialized pain-sensing neurons densely innervate the skin and can be activated by various immune mediators. There are several distinct populations of immune cells found primarily in the skin, many of which are activated within seconds after tissue injury. However, their contribution to the pain response remains unknown. We hypothesize that these tissue-resident immune cells play an important and previously unappreciated role in the pain response. The goal of this study is to identify those cells and their secreted mediators that are capable of activating pain-sensing neurons. These studies have the potential to transform our understanding of neuro-immune interactions and identify new mechanisms underlying pain.