Chemokines and the pathophysiology of neuropathic pain

*Departments of Cell Biology, Neurobiology and Anatomy, and Anesthesiology, Loyola University Chicago, Maywood, IL 60626; and
^†Molecular Pharmacology and Structural Biochemistry, Northwestern University, Chicago, IL 60611

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved October 18, 2007 (received for review September 28, 2007)

Abstract

Chemokines and chemokine receptors are widely expressed by cells of the immune and nervous systems. This review focuses on our current knowledge concerning the role of chemokines in the pathophysiology of chronic pain syndromes. Injury- or disease-induced changes in the expression of diverse chemokines and their receptors have been demonstrated in the neural and nonneural elements of pain pathways. Under these circumstances, chemokines have been shown to modulate the electrical activity of neurons by multiple regulatory pathways including increases in neurotransmitter release through Ca-dependent mechanisms and transactivation of transient receptor channels. Either of these mechanisms alone, or in combination, may contribute to sustained excitability of primary afferent and secondary neurons within spinal pain pathways. Another manner in which chemokines may influence sustained neuronal excitability may be their ability to function as excitatory neurotransmitters within the peripheral and central nervous system. As is the case for traditional neurotransmitters, injury-induced up-regulated chemokines are found within synaptic vesicles. Chemokines released after depolarization of the cell membrane can then act on other chemokine receptor-bearing neurons, glia, or immune cells. Because up-regulation of chemokines and their receptors may be one of the mechanisms that directly or indirectly contribute to the development and maintenance of chronic pain, these molecules may then represent novel targets for therapeutic intervention in chronic pain states.

Footnotes

^‡To whom correspondence should be addressed. E-mail: r-miller10{at}northwestern.edu
Author contributions: F.A.W., H.J., and R.J.M. designed research; F.A.W. and H.J. performed research; and F.A.W., H.J., and R.J.M. analyzed data and wrote the paper.
The authors declare no conflict of interest.
↵ § White F, Bauer W, Jellish W, Chan D, LaMotte R, Miller R, 25th Annual Scientific Meeting of the American Pain Society, May 3–6, 2006, San Antonio, TX, poster 682.