期刊
JOURNAL OF PAIN
卷 14, 期 1, 页码 24-35出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.jpain.2012.09.015
关键词
CCL5 receptor antagonists; inflammation; Met-RANTES; neuropathic pain; nociception
资金
- Chang Gung Memorial Hospital at Lin-Kou [CMRPG392171, CMRPG381183]
- Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
The C-C motif chemokine ligand 5 (CCL5; also known as regulated on activation, normal T expressed and secreted, or RANTES) is a member of the CC family of chemokines that specifically attract and activate leukocytes to sites of inflammation. Although CCL5 has been implicated in the processing of pain, its detailed mechanisms of action are still unknown. In this study, we investigated the potential of the Met-RANTES, a selective CCL5 receptor antagonist, via peritoneal administration to modulate the recruitment of inflammatory cells in injured sites and attenuate nociceptive responses in a neuropathic pain model in mice. Nociceptive sensitization, immune cell infiltration, multiple cytokine secretion, and opioid peptide expression in damaged nerves were studied. Our results indicated that Met-RANTES-treated mice had less behavioral hypersensitivity after partial sciatic nerve ligation. Macrophage infiltration, pro-inflammatory cytokine (TNF alpha, IL-1 beta, IL-6, and IFN gamma) protein secretion, and enkephalin, beta-endorphin, and dynorphin mRNA expression in damaged nerves following partial sciatic nerve ligation were significantly decreased, and anti-inflammatory cytokine (IL-10) protein was significantly increased in Met-RANTES-treated mice. These results suggest that CCL5 is capable of regulating the microenvironment that controls behavioral hypersensitivity at the level of the peripheral injured site in a murine chronic neuropathic pain model. Perspective: The present study identifies the potent pro-inflammatory potential of CCL5 and verifies the possible role of selective CCL5 receptor inhibitor in a murine neuropathic pain model. (C) 2013 by the American Pain Society
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