title: Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto University of Sao Paulo, Brazil.
authors.forename: E U
authors.initials: EU
authors.lastname: Carreira
authors.forename: V
authors.initials: V
authors.lastname: Carregaro
authors.forename: M M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: A
authors.initials: A
authors.lastname: Moriconi
authors.forename: A
authors.initials: A
authors.lastname: Aramini
authors.forename: W A
authors.initials: WA
authors.lastname: Verri
authors.forename: S H
authors.initials: SH
authors.lastname: Ferreira
authors.forename: F Q
authors.initials: FQ
authors.lastname: Cunha
authors.forename: T M
authors.initials: TM
authors.lastname: Cunha
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006930:Hyperalgesia / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010149:Postoperative Pain / Q000276:immunology* / Q000503:physiopathology; D023062:Receptors, Interleukin-8A / Q000037:antagonists & inhibitors / Q000276:immunology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D054360:Chemokine CXCL1; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B