Complement receptor C5aR1 signaling in sensory neuron-associated macrophages drives neuropathic pain
Complement receptor C5aR1 signaling in sensory neuron-associated macrophages drives neuropathic pain
Abstract Neuroimmune interactions across the pain pathway play a predominant role in the development of neuropathic pain. Previous reports demonstrated that complement driven effector systems including the C5a/C5aR1 axis contribute to these neuro-immune mechanisms. However, the cellular and molecular mechanisms underlying C5a/C5aR1 signaling-mediated neuropathic pain development remain ill-identified. Here we show that neuropathic pain following peripheral nerve injury was attenuated in C5aR1-deficient male and female mice as well as in wild type mice treated with a selective allosteric C5aR1 antagonist. Using two complementary cell-specific C5aR1 knockout mouse strains, we identified C5a/C5aR1 driven-activation of sensory neuron-associated macrophages (sNAMs) located in the sensory ganglia as the key site of peripheral nerve injury-induced neuropathic pain, whereas activation of macrophages of the local of peripheral nerve injury was not involved. Mechanistically, we uncovered IL-1b the main mediator of pain hypersensitivity in response to C5aR1 signaling in sNAMs. Our findings highlight a crucial role of C5a/C5aR1 axis activation in sNAMs for the development of neuropathic pain and identify this pathway as a promising novel target for neuropathic pain therapy.
Lopes Alexandre H. P.、Berta Temugin、K?hl J?rg、Cunha Thiago M.、Damasceno Samara、Quadros Andreza U.、Sagar Devi R.、Lee Sang Hoon、Maganin Alexandre G. M.、Brandolini Laura、Davoli-Ferreira Marcela、Chapman Victoria、Cunha Fernando Q.、Silva Concei??o E. A.、Alves-Filho Jose C.、Allegretti Marcello、Cavallini Maria C. M.
Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo||Graduate Program in Pharmacology Ribeirao Preto Medical School, University of Sao PauloPain Research Center, Department of Anesthesiology, University of Cincinnati College of MedicineInstitute for Systemic Inflammation Research, University of L¨1beck||Division of Immunobiology, Cincinnati Children?ˉs Hospital Medical Center and University of Cincinnati College of MedicineCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao PauloCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao PauloCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo||Graduate Program in Pharmacology Ribeirao Preto Medical School, University of Sao PauloPain Centre Versus Arthritis, School of Life Sciences, University of Nottingham, Clinical Sciences Building City HospitalPain Research Center, Department of Anesthesiology, University of Cincinnati College of MedicineCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo||Graduate Program in Pharmacology Ribeirao Preto Medical School, University of Sao PauloR&D Department, Domp¨| Farmaceutici s.p.a.Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo||Graduate Program in Basic and Applied Immunology Ribeirao Preto Medical School, University of Sao PauloPain Centre Versus Arthritis, School of Life Sciences, University of Nottingham, Clinical Sciences Building City HospitalCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao PauloCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo||Graduate Program in Basic and Applied Immunology Ribeirao Preto Medical School, University of Sao PauloCenter for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao PauloR&D Department, Domp¨| Farmaceutici s.p.a.Center for Research in Inflammatory Diseases (CRID), Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo||Graduate Program in Basic and Applied Immunology Ribeirao Preto Medical School, University of Sao Paulo
神经病学、精神病学基础医学生理学
neuropathic paincomplement systemmacrophagesC5aR1IL-1b
Lopes Alexandre H. P.,Berta Temugin,K?hl J?rg,Cunha Thiago M.,Damasceno Samara,Quadros Andreza U.,Sagar Devi R.,Lee Sang Hoon,Maganin Alexandre G. M.,Brandolini Laura,Davoli-Ferreira Marcela,Chapman Victoria,Cunha Fernando Q.,Silva Concei??o E. A.,Alves-Filho Jose C.,Allegretti Marcello,Cavallini Maria C. M..Complement receptor C5aR1 signaling in sensory neuron-associated macrophages drives neuropathic pain[EB/OL].(2025-03-28)[2025-08-09].https://www.biorxiv.org/content/10.1101/2022.07.01.498487.点此复制
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