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.
%0 Journal Article
%1 Dansereau2008
%A Dansereau, Marc-André
%A Gosselin, Romain-Daniel
%A Pohl, Michel
%A Pommier, Blandine
%A Mechighel, Patricia
%A Mauborgne, Annie
%A Rostene, William
%A Kitabgi, Patrick
%A Beaudet, Nicolas
%A Sarret, Philippe
%A Melik-Parsadaniantz, Stéphane
%D 2008
%J J Neurochem
%K genetics/metabolism;TRPVCationChannels antagonists/&/inhibitors;SpinalCord genetics/metabolism;Enzyme-LinkedImmunosorbentAssay Sprague-Dawley;Receptors genetics/metabolism;Calcium AnalysisofVariance;Animals;Behavior Afferent drugeffects;PotassiumChloride cytology;SubcellularFractions drugeffects;PainThreshold methods;Ganglia genetics/metabolism pharmacology;Pyrrolidines drugeffects/metabolism;SubstanceP Animal;CalcitoninGene-RelatedPeptide cytology;GeneExpressionRegulation metabolism;ChemokineCCL2 CCR2 physiopathology;Male;Neurons drugeffects;Hyperalgesia pharmacology;Rats;Rats Spinal
%N 2
%P 757--769
%R 10.1111/j.1471-4159.2008.05429.x
%T Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats.
%U http://dx.doi.org/10.1111/j.1471-4159.2008.05429.x
%V 106
%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.
@article{Dansereau2008,
abstract = {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.},
added-at = {2011-08-01T21:20:34.000+0200},
author = {Dansereau, Marc-André and Gosselin, Romain-Daniel and Pohl, Michel and Pommier, Blandine and Mechighel, Patricia and Mauborgne, Annie and Rostene, William and Kitabgi, Patrick and Beaudet, Nicolas and Sarret, Philippe and Melik-Parsadaniantz, Stéphane},
biburl = {https://www.bibsonomy.org/bibtex/2f96c723f21618dea48a78a73dac1ea23/crc_chus},
doi = {10.1111/j.1471-4159.2008.05429.x},
institution = {Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada.},
interhash = {b04bf0aecbe7554843ce861c2a92a277},
intrahash = {f96c723f21618dea48a78a73dac1ea23},
journal = {J Neurochem},
keywords = {genetics/metabolism;TRPVCationChannels antagonists/&/inhibitors;SpinalCord genetics/metabolism;Enzyme-LinkedImmunosorbentAssay Sprague-Dawley;Receptors genetics/metabolism;Calcium AnalysisofVariance;Animals;Behavior Afferent drugeffects;PotassiumChloride cytology;SubcellularFractions drugeffects;PainThreshold methods;Ganglia genetics/metabolism pharmacology;Pyrrolidines drugeffects/metabolism;SubstanceP Animal;CalcitoninGene-RelatedPeptide cytology;GeneExpressionRegulation metabolism;ChemokineCCL2 CCR2 physiopathology;Male;Neurons drugeffects;Hyperalgesia pharmacology;Rats;Rats Spinal},
language = {eng},
medline-pst = {ppublish},
month = Jul,
number = 2,
pages = {757--769},
pii = {JNC5429},
pmid = {18419759},
timestamp = {2011-08-01T21:20:34.000+0200},
title = {Spinal CCL2 pronociceptive action is no longer effective in CCR2 receptor antagonist-treated rats.},
url = {http://dx.doi.org/10.1111/j.1471-4159.2008.05429.x},
volume = 106,
year = 2008
}