Neutrophil recruitment mediated by the CXCL1/KC chemokine and its receptors CXCR1/CXCR2 plays a critical role in inflammatory diseases. Recently, neutrophil migration and activation triggered by CXCL1-CXCR1/2 signalling was implicated in inflammatory nociception; however, their role in post-surgical pain has not been elucidated. In this study, we addressed the function of neutrophils in the genesis of post-incisional pain in an experimental model of post-surgical pain.


Mechanical hyperalgesia was determined with an electronic von Frey test in a mouse hindpaw incisional model. Neutrophil accumulation and the level of CXCL1/KC in the plantar tissue were determined by myeloperoxidase activity assay and enzyme-linked immunosorbent assay, respectively.


An incision in the mouse hindpaw produces long-lasting mechanical hyperalgesia that persists for at least 72 h after surgery. Following surgery, there was an increase in both neutrophil accumulation and the CXCL1/KC level in the incised paws. The depletion of the mouse neutrophils by vinblastine sulphate or anti-neutrophil antibody treatments reduced the mechanical hyperalgesia after paw incision. Furthermore, the treatment of mice with ladarixin, an orally acting CXCR1/2 antagonist, also reduced both the mechanical hyperalgesia and the infiltration of neutrophils in the incised paws.


In conclusion, it appears that after surgical processes, neutrophils are recruited by CXCL1-CXCR1/2 signalling and participate in the cascade of events, leading to mechanical hyperalgesia. These results suggest that blocking neutrophil migration through the inhibition of CXCL1-CXCR1/2 signalling might be a target to control post-surgical pain.