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• W2000409826 startingPage "1053" @default.
• W2000409826 abstract "Many pain syndromes are associated with abnormal proliferation of peripheral sensory fibers. We showed previously that angiotensin II, acting through its type 2 receptor (AT2), stimulates axon outgrowth by cultured dorsal root ganglion neurons. In this study, we assessed whether AT2 mediates nociceptor hyperinnervation in the rodent hind paw model of inflammatory pain. Plantar injection of complete Freund's adjuvant (CFA), but not saline, produced marked thermal and mechanical hypersensitivity through 7 days. This was accompanied by proliferation of dermal and epidermal PGP9.5-immunoreactive (ir) and calcitonin gene-related peptide-immunoreactive (CGRP-ir) axons, and dermal axons immunoreactive for GFRα2 but not tyrosine hydroxylase or neurofilament H. Continuous infusion of the AT2 antagonist PD123319 beginning with CFA injection completely prevented hyperinnervation as well as hypersensitivity over a 7-day period. A single PD123319 injection 7 days after CFA also reversed thermal hypersensitivity and partially reversed mechanical hypersensitivity 3 hours later, without affecting cutaneous innervation. Angiotensin II-synthesizing proteins renin and angiotensinogen were largely absent after saline but abundant in T cells and macrophages in CFA-injected paws with or without PD123319. Thus, emigrant cells at the site of inflammation apparently establish a renin-angiotensin system, and AT2 activation elicits nociceptor sprouting and heightened thermal and mechanical sensitivity.Short-term AT2 activation is a potent contributor to thermal hypersensitivity, whereas long-term effects (such as hyperinnervation) also contribute to mechanical hypersensitivity. Pharmacologic blockade of AT2 signaling represents a potential therapeutic strategy aimed at biologic mechanisms underlying chronic inflammatory pain." @default.
• W2000409826 created "2016-06-24" @default.
• W2000409826 creator A5005700238 @default.
• W2000409826 creator A5082768258 @default.
• W2000409826 creator A5091086352 @default.
• W2000409826 date "2013-10-01" @default.
• W2000409826 modified "2023-10-12" @default.
• W2000409826 title "Angiotensin II Receptor Type 2 Activation Is Required for Cutaneous Sensory Hyperinnervation and Hypersensitivity in a Rat Hind Paw Model of Inflammatory Pain" @default.
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• W2000409826 doi "https://doi.org/10.1016/j.jpain.2013.04.002" @default.
• W2000409826 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3971648" @default.
• W2000409826 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23726047" @default.
• W2000409826 hasPublicationYear "2013" @default.
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