Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation

Chronic postsurgical pain (CPSP) is a global concern associated with significant health and economic issues for patients. We investigated the effects of C-X-C motif chemokine receptor 2 (CXCR2) related signal transduction mechanisms on CPSP in a rat skin muscle incision and retraction (SMIR) model. Following model establishment, glial cells in the spinal dorsal horn were activated, and the expression of inflammatory factors (tumor necrosis factor (TNF)-α and interleukin (IL)-1β increased. The SMIR group demonstrated elevated expression of CXCR2, phosphorylated ERK (p-ERK), and phosphorylated p38 (p-p38) in the spinal dorsal horn. After intrathecal injection of the CXCR2 antagonist SB225002, the rats' pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation. Additionally, primary microglial cells induced by lipopolysaccharide were used as an in vitro model. Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP.