CCL2 is a key mediator of microglia activation in neuropathic pain states.
While neuroimmune interactions are increasingly recognized as important in nociceptive processing, the nature and functional significance of these interactions is not well defined. There are multiple reports that the activation of spinal microglia is a critical event in the generation of neuropathic pain behaviors but the mediators of this activation remain disputed. Here we show that the chemokine CCL2, produced by both damaged and undamaged primary sensory neurons in neuropathic pain states in rats, is released in an activity dependent manner from the central terminals of these fibres. We also demonstrate that intraspinal CCL2 in naïve rats leads to activation of spinal microglia and neuropathic pain-like behavior. An essential role for spinal CCL2 is demonstrated by the inhibition of neuropathic pain behavior and microglial activation by a specific neutralising antibody to CCL2 administered intrathecally. Thus, the neuronal expression of CCL2 provides a mechanism for immune activation, which in turn regulates the sensitivity of pain signaling systems in neuropathic pain states.
Neurorestoration group, Wolfson Centre for Age Related Diseases, Kings College London, Wolfson Wing, Hodgkin Building, Guy's Campus, London, London, UK.
Michael A
MA
Thacker
Anna K
AK
Clark
Thomas
T
Bishop
John
J
Grist
Ping K
PK
Yip
Lawrence D F
LD
Moon
Stephen W N
SW
Thompson
Fabien
F
Marchand
Stephen B
SB
McMahon
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002633:Chemotaxis / Q000276:immunology; D004195:Disease Models, Animal; D005911:Gliosis / Q000276:immunology* / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000276:immunology*; D009437:Neuralgia / Q000276:immunology* / Q000503:physiopathology; D009619:Nociceptors / Q000276:immunology / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000276:immunology* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000276:immunology / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology
D000906:Antibodies; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2