Macrophage angiotensin II type 2 receptor triggers neuropathic pain. Proc Natl Acad Sci U S A 2018 Aug 21;115(34):E8057-E8066
Date
08/08/2018Pubmed ID
30082378Pubmed Central ID
PMC6112686DOI
10.1073/pnas.1721815115Scopus ID
2-s2.0-85051790113 (requires institutional sign-in at Scopus site) 101 CitationsAbstract
Peripheral nerve damage initiates a complex series of structural and cellular processes that culminate in chronic neuropathic pain. The recent success of a type 2 angiotensin II (Ang II) receptor (AT2R) antagonist in a phase II clinical trial for the treatment of postherpetic neuralgia suggests angiotensin signaling is involved in neuropathic pain. However, transcriptome analysis indicates a lack of AT2R gene (Agtr2) expression in human and rodent sensory ganglia, raising questions regarding the tissue/cell target underlying the analgesic effect of AT2R antagonism. We show that selective antagonism of AT2R attenuates neuropathic but not inflammatory mechanical and cold pain hypersensitivity behaviors in mice. Agtr2-expressing macrophages (MΦs) constitute the predominant immune cells that infiltrate the site of nerve injury. Interestingly, neuropathic mechanical and cold pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral MΦs and AT2R-null hematopoietic cell transplantation. Our study identifies AT2R on peripheral MΦs as a critical trigger for pain sensitization at the site of nerve injury, and therefore proposes a translatable peripheral mechanism underlying chronic neuropathic pain.
Author List
Shepherd AJ, Mickle AD, Golden JP, Mack MR, Halabi CM, de Kloet AD, Samineni VK, Kim BS, Krause EG, Gereau RW 4th, Mohapatra DPAuthor
Aaron David Mickle PhD Associate Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AllograftsAnimals
Chronic Pain
Hematopoietic Stem Cell Transplantation
Macrophages
Mice
Neuralgia
Receptor, Angiotensin, Type 2
