Neuropathic pain occurs as a result of damage and/or inflammation in the nervous system and presents as severe chronic pain. Neuroinflammation mediated by chemokines may be associated with the pathogenesis of neuropathic pain. Kiguchi et al. investigated the roles of the C-X-C chemokine ligand type 2 [macrophage inflammatory protein 2 (MIP-2)] and C-X-C chemokine receptor type 2 (CXCR2) in nerve injury-induced neuropathic pain. Expression of MIP-2 and CXCR2 were up-regulated and localized on accumulated neutrophils and macrophages in the injured sciatic nerve (SCN) after partial sciatic nerve ligation (PSL). MIP-2-neutralizing antibody or the CXCR2 antagonist N-(2-bromophenyl)-N′-(2-hydroxy-4-nitrophenyl)urea (SB225002) prevented PSL-induced tactile allodynia and thermal hyperalgesia. Both anti-MIP-2 and SB225002 suppressed up-regulation of inflammatory cytokines and chemokines in the injured SCN. Acetylation of histone H3 (AcK9-H3) on the promoter region of MIP-2 and CXCR2 was increased in the injured SCN after PSL. This study demonstrates that expression of MIP-2 and CXCR2 was up-regulated by epigenetic histone H3 acetylation in recruited macrophages and neutrophils localized in the injured peripheral nerves. Augmentation of the MIP-2/CXCR2 axis recruited neutrophils into the injured nerves and elicited neuroinflammation, which leads to neuropathic pain, suggesting that the MIP-2/CXCR2 axis could be a possible therapeutic target for the treatment of neuropathic pain.
See article at J Pharmacol Exp Ther 2012, 340:577–587.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics