CD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.

TitleCD11b+Ly6G- myeloid cells mediate mechanical inflammatory pain hypersensitivity.
Publication TypeJournal Article
Year of Publication2015
AuteursGhasemlou, N, Chiu, IM, Julien, J-P, Woolf, CJ
JournalProc Natl Acad Sci U S A
Date Published2015 Dec 08
KeywordsAnimals, Antigens, Ly, CD11b Antigen, Chemokines, Cytokines, Freund's Adjuvant, Inflammation, Male, Mice, Mice, Inbred C57BL, Myeloid Cells, Neutrophils, Pain

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID26598697
PubMed Central IDPMC4679057
Grant ListK22 AI114810 / AI / NIAID NIH HHS / United States
R37 NS039518 / NS / NINDS NIH HHS / United States
5R37NS039518-13 / NS / NINDS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada