Neutrophil dynamics in surgical wounds – A novel role of interleukin-7

Abstract

Postoperative pain and consequently chronic postsurgical pain remain a significant burden among patients. While neutrophilic granulocytes (neutrophils) are known to play a critical role in wound healing, their precise contribution to pain modulation is not fully understood. The neurotrophin nerve growth factor (NGF), released by fibroblasts and immune cells following injury, is an early mediator of pain development. A companion paper demonstrated that NGF administration to axons of cultured sensory neurons in microfluidic chambers induces upregulation of Il7, encoding interleukin-7 (IL-7). However, its role in neutrophil dynamics within surgical wounds remains broadly unclear. In a murine model of laparotomy, we observed that IL-7 was expressed at wound sites and co-localized with sensory nerve endings and infiltrating neutrophils within 24 h post-surgery. Laparotomy triggered neutrophil mobilization from the bone marrow, leading to an influx of both mature and immature neutrophils into the circulation. Flow cytometric analysis further revealed IL-7 receptor (IL-7R) surface expression on neutrophils, with IL-7 stimulation also enhancing the expression of activation and maturation markers on neutrophils in vitro. These findings suggest that NGF-induced IL-7 release from peripheral nerve terminals represents a novel neuroinflammatory mechanism modulating neutrophil dynamics in the surgical wound, potentially impairing wound healing and exacerbating pain. Therefore, targeting IL-7 signalling in peripheral nerves may offer a promising strategy for improving postoperative pain management.