Chemokines as pain mediators and modulators.
OBJECTIVE
Chemokines are central to the innate immune response following tissue damage, injury and some diseases. The function of chemokines in nervous system autoimmune diseases has been long recognized. There is also growing evidence that disease-associated or injury-induced functional expression of chemokines/receptors in both neural and nonneural elements of the peripheral nervous system play crucial roles in the pathophysiology of chronic pain.


RESULTS
Chemokine involvement in neuropathic pain processing has recently been established in animal models. Evidence of chemokine contribution to chronic pain includes the upregulation of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its respective receptor, CCR2, in many subpopulations of sensory neurons. Activation of CCR2 by MCP-1 elicits membrane depolarization, triggers action potentials and sensitizes nociceptors via transactivation of transient receptor potential channels TRPA1 and TRPV1. Increased signaling by stromal-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, has been shown to contribute to chronic pain behavior. The use of specific chemokine receptor antagonists for CCR2 and CXCR4 successfully reverses nociceptive pain behavior.


CONCLUSIONS
Our results suggest that specific chemokines/receptors are upregulated by sensory neurons following peripheral nerve injury and appear to participate in neural signal processing leading to chronic pain states. Taken together, chemokines and their receptors are potential targets for development of novel therapeutics.
White
Fletcher A
FA
Department of Cell Biology, Loyola University - Chicago, Maywood, Illinois 60153, USA. fwhite@lumc.edu
Wilson
Natalie M
NM
D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009437:Neuralgia / Q000209:etiology / Q000503:physiopathology*; D009457:Neuroglia / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D019707:Receptors, Chemokine / Q000378:metabolism*; D015398:Signal Transduction
D018925:Chemokines; D019707:Receptors, Chemokine
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