title: P-selectin is required for neutrophils and macrophage infiltration into injured site and contributes to generation of behavioral hypersensitivity following peripheral nerve injury in mice.
abstract: Growing evidence suggests that leukocyte extravasation is initiated by the interaction of selectins with their ligands; as well as an essential role for P-selectin in the initial recruitment of inflammatory cells to sites of inflammation. In this study, P-selectin-deficient (P-sel-/-) mice were used to test the hypothesis that lack of P-selectin would attenuate the recruitment of inflammatory cells to the site of inflammation, thereby modulating pain in a murine chronic neuropathic pain model. Nociceptive sensitization and the microenvironment of the peripheral injury site were studied in wild-type (P-sel+/+) and P-selectin-deficient (P-sel-/-) mice after partial sciatic nerve ligation (PSNL). Variables measured included myeloperoxidase (MPO) activity, several inflammatory cell infiltration profiles, cytokines, and endogenous opioid peptide expression in damaged nerves. Results indicate that behavioral hypersensitivity, MPO activity, and infiltration of neutrophils and macrophages were attenuated in P-sel-/- mice after PSNL. Proinflammatory cytokines, tumor necrosis factor α, and interleukin (IL)-6, were reduced in damaged nerves following PSNL; however, several antiinflammatory cytokines - IL-1Ra, IL-4, and IL-10 - were significantly increased in P-sel-/- mice. In addition, endogenous opioid peptides mRNA was significantly lower in P-sel-/- mice compared with P-sel +/+ mice. The current results demonstrated that the absence of P-selectin in mice leads to an altered microenvironment that attenuated behavioral hypersensitivity. The specific role of P-selectin could have been a result of decreased neutrophils, as well as the accumulation of macrophages at the site of injury, which may subsequently modulate the inflammatory cytokine expression and impact behavioral hypersensitivity within the injured nerve.
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC Transgenic & Molecular Immunogenetics Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC Department of Medicine, Chang Gung University, Linkou, Taiwan, ROC Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou, Taiwan, ROC Graduate Institutes of Clinical Medical Sciences, Chang Gung University, Linkou, Taiwan, ROC Department of Anesthesiology, National Defense Medical Center and Tri-Service General Hospital, Taipei, Taiwan, ROC.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Liou
authors.forename: Chiou-Mei
authors.initials: CM
authors.lastname: Lee
authors.forename: Yi-Chiao
authors.initials: YC
authors.lastname: Lin
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Chia-Chih
authors.initials: CC
authors.lastname: Liao
authors.forename: Hung-Chen
authors.initials: HC
authors.lastname: Lee
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000502:physiology*; D009504:Neutrophils / Q000473:pathology*; D019007:P-Selectin / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D019007:P-Selectin
keywords: Animal model; Inflammation; Nerve injury; Neuropathic pain; P-selectin