Peritoneal Administration of Met-RANTES Attenuates Inflammatory and Nociceptive Responses in a Murine Neuropathic Pain Model
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- 作者：Jiin-Tarng Liou ; Chih-Chieh Mao ; Daniel Ching-Wah Sum ; Fu-Chao Liu ; Ying-Shu Lai ; Jui-Chin Li ; Yuan-Ji Day ; yd3j@adm.cgmh.org.tw
- 关键词：CCL5 receptor antagonists ; inflammation ; Met-RANTES ; neuropathic pain ; nociception
- 刊名：The Journal of Pain
- 出版年：2013
- 出版时间：January, 2013
- 年：2013
- 卷：14
- 期：1
- 页码：24-35
- 全文大小：1276 K
文摘
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¦Á, IL-1¦Â, IL-6, and IFN¦Ã) protein secretion, and enkephalin, ¦Â-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.