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Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats.

Authors: Dansereau, MA  Gosselin, RD  Pohl, M  Pommier, B  Mechighel, P  Mauborgne, A  Rostene, W  Kitabgi, P  Beaudet, N  Sarret, P  Melik-Parsadaniantz, S 
Citation: Dansereau MA, etal., J Neurochem. 2008 Jul;106(2):757-69. Epub 2008 Apr 17.
Pubmed: (View Article at PubMed) PMID:18419759
DOI: Full-text: DOI:10.1111/j.1471-4159.2008.05429.x

A better understanding of the mechanisms linked to chemokine pronociceptive effects is essential for the development of new strategies to better prevent and treat chronic pain. Among chemokines, MCP-1/CCL2 involvement in neuropathic pain processing is now established. However, the mechanisms by which MCP-1/CCL2 exerts its pronociceptive effects are still poorly understood. In the present study, we demonstrate that MCP-1/CCL2 can alter pain neurotransmission in healthy rats. Using immunohistochemical studies, we first show that CCL2 is constitutively expressed by primary afferent neurons and their processes in the dorsal horn of the spinal cord. We also observe that CCL2 is co-localized with pain-related peptides (SP and CGRP) and capsaicin receptor (VR1). Accordingly, using in vitro superfusion system of lumbar dorsal root ganglion and spinal cord explants of healthy rats, we show that potassium or capsaicin evoke calcium-dependent release of CCL2. In vivo, we demonstrate that intrathecal administration of CCL2 to healthy rats produces both thermal hyperalgesia and sustained mechanical allodynia (up to four consecutive days). These pronociceptive effects of CCL2 are completely prevented by the selective CCR2 antagonist (INCB3344), indicating that CCL2-induced pain facilitation is elicited via direct spinal activation of CCR2 receptor. Therefore, preventing the activation of CCR2 might provide a fruitful strategy for treating pain.


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RGD Object Information
RGD ID: 2307043
Created: 2009-05-15
Species: All species
Last Modified: 2009-05-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.