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Exp Neurol. 2005 Apr;192(2):444-62.

Immune and glial cell factors as pain mediators and modulators.

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  • 1Neurorestoration Group and London Pain Consortium, Wolfson Wing, Hodgkin Building, Guy's Campus, King's College London, London Bridge, London, SE1 1UL, UK.


A decade ago the attention of pain scientists was focused on a small number of molecules such as prostaglandin and bradykinin as peripheral pain mediators or modulators. These factors were known to be produced by tissue damage or inflammation, and considered responsible for the activation and sensitization of peripheral pain signaling sensory neurons. A small number of molecules were also identified as central pain mediators, most notably glutamate and substance P released from central nociceptive nerve terminals, and, starting at that time, appreciation that nitric oxide might be produced by dorsal horn neurons and act as a diffusible transmitter to increase excitability of central pain circuits. During the last decade evidence has emerged for many novel pain mediators. The old ones have not disappeared, although their roles have been redefined in some cases. Prostaglandin E2 (PGE2), for instance, is now recognized as playing a prominent role in CNS as well as peripheral tissues. The newly identified mediators include a variety of factors produced and released from nonneuronal cells-predominantly immune and glial cells. The evidence is now growing apace that these are important mediators of persistent pain states and can act at a number of loci. Here we review the actions of several of these factors-the pro-inflammatory cytokines, some chemokines, and some neurotrophic factors, which, in addition to their traditionally recognized roles, are all capable of changing the response properties of peripheral and central pain signaling neurons. We review these actions, first in periphery, where a substantial literature has accumulated, and then in spinal cord, where the role of factors from nonneuronal cells has only recently been identified as of considerable importance.

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