title: CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.
abstract: Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant- and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G(+)CD11b(+) neutrophils and T-cell receptor (TCR) β(+) T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b(+)Ly6G(-) myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2(+)Ly6C(hi)) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b(+)Ly6G(-) myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.
authors.affiliation: F. M. Kirby Neurobiology Center, Boston Children's Hospital & Harvard Medical School, Boston, MA 02115;
authors.forename: Nader
authors.initials: N
authors.lastname: Ghasemlou
authors.affiliation: F. M. Kirby Neurobiology Center, Boston Children's Hospital & Harvard Medical School, Boston, MA 02115; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;
authors.forename: Isaac M
authors.initials: IM
authors.lastname: Chiu
authors.affiliation: Research Centre of Institut Universitaire en Santé Mentale de Québec and Department of Psychiatry and Neuroscience, Laval University, Quebec City, QC, Canada G1J 2G3.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
authors.affiliation: F. M. Kirby Neurobiology Center, Boston Children's Hospital & Harvard Medical School, Boston, MA 02115; clifford.woolf@childrens.harvard.edu.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000032:analysis*; D039481:CD11b Antigen / Q000032:analysis*; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D005620:Freund's Adjuvant / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010146:Pain / Q000503:physiopathology*
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; D018925:Chemokines; D016207:Cytokines; C480309:Ly6G antigen, mouse; D005620:Freund's Adjuvant
keywords: cytokines; inflammation; macrophages; monocytes; pain