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Angiotensin receptor type 2 mediates hypersensitivity and hyperinnervation in an inflammatory pain model
Author(s) -
SMITH PETER G,
LIAO ZHAOHUI,
CHAKRABARTY ANURADHA
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb568
Subject(s) - nociceptor , dorsal root ganglion , medicine , angiotensin ii , endocrinology , nociception , hyperalgesia , saline , renin–angiotensin system , receptor , anatomy , dorsum , blood pressure
Abnormal sensory axon proliferation occurs in many pain syndromes. The objective of this study was to determine if the angiotensin type 2 receptor (AT2), a mediator of dorsal root ganglion axon sprouting, is required for increased innervation density and hypersensitivity in a rat hind paw model of inflammatory pain. Injection of complete Freund's adjuvant (CFA), but not saline, produced marked thermal and mechanical hypersensitivity through 7 days, accompanied by proliferation of cutaneous axons immunoreactive for the pan‐neuronal marker PGP9.5, calcitonin gene‐related peptide (a marker of heat‐sensitive nociceptors) and GFRα2 (a marker of mechanosensitive nociceptors). Continuous infusion of the AT2 antagonist PD123319 beginning with CFA injection completely prevented hyperinnervation and hypersensitivity. 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. We conclude that emigrant inflammatory cells establish a renin‐angiotensin system, which leads to AT2 activation required for nociceptor sprouting and heightened thermal and mechanical sensitivity. Supported by HD049615.