Neutrophils recruited by <scp>CXCR1/2</scp> signalling mediate post‐incisional pain

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Neutrophil recruitment mediated by the <jats:styled-content style="fixed-case">CXCL1/KC</jats:styled-content> chemokine and its receptors <jats:styled-content style="fixed-case">CXCR1/CXCR2</jats:styled-content> plays a critical role in inflammatory diseases. Recently, neutrophil migration and activation triggered by <jats:styled-content style="fixed-case">CXCL1‐CXCR1/2</jats:styled-content> 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Mechanical hyperalgesia was determined with an electronic von Frey test in a mouse hindpaw incisional model. Neutrophil accumulation and the level of <jats:styled-content style="fixed-case">CXCL1/KC</jats:styled-content> in the plantar tissue were determined by myeloperoxidase activity assay and enzyme‐linked immunosorbent assay, respectively.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 <jats:styled-content style="fixed-case">CXCL1/KC</jats:styled-content> 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 <jats:styled-content style="fixed-case">CXCR1/2</jats:styled-content> antagonist, also reduced both the mechanical hyperalgesia and the infiltration of neutrophils in the incised paws.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In conclusion, it appears that after surgical processes, neutrophils are recruited by <jats:styled-content style="fixed-case">CXCL1‐CXCR1/2</jats:styled-content> signalling and participate in the cascade of events, leading to mechanical hyperalgesia. These results suggest that blocking neutrophil migration through the inhibition of <jats:styled-content style="fixed-case">CXCL1‐CXCR1/2</jats:styled-content> signalling might be a target to control post‐surgical pain.</jats:p></jats:sec>