The Impact of Neutrophils on the Resolution of Post-Surgical Pain 2306258

Abstract Introduction It is well established that the immune system contributes to the development of chronic pain, however the intricacies of how the immune system, specifically neutrophils, could also aid in the resolution of pain remains elusive. The aim of this study is to investigate the role of neutrophils on post-surgical pain resolution and gain a better understanding of how they interact with and influence other immune cells to mediate post-surgical pain. Methods By employing a well-established surgical injury model via plantar incision, we investigated the impact of depleting neutrophils on pain sensitivity following surgery, as well as the effect on the immune response. To deplete neutrophils systemically, α-Ly6G was injected intraperitoneally every three days following injury. Mechanical pain was assessed using the von Frey method over the course of two weeks. After surgical injury, the incised skin was collected and processed for the following biological assays: cytokine array, toluidine blue staining, and flow cytometry. Results We validated the efficacy of α-Ly6G injections to deplete neutrophils in the blood and in the skin using flow cytometry. Neutrophil depleted mice showed prolonged pain following surgical incision compared to the control group. In addition, the neutrophil depleted mice have altered cytokine expression with a notable increase in IL-4, a cytokine primarily released by mast cells, and increased mast cell presence and degranulation in the incised skin. Conclusion We have found that neutrophils play a crucial role in the transition from acute to chronic pain. This transition may be mediated by mast cell activity in the paw skin. The presence of neutrophils could be essential to preventing excessive mast cell activity and preventing prolonged pain following surgical injury. Funding Source NIH and DOD Topic Categories Neuroimmunology (NEUR)