Microglia, Complement, and Neuropathic Pain

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Microglia, Complement, and Neuropathic Pain

http://www.medicalnewstoday.com/articles/79114.php

S. , Costigan, J. Brenner, Chi Him Eddie

Ma, Joachim Scholz, Moss, J. Allchorne, L.

Stahl, and Clifford J. Woolf

In this week's Journal, et al. used microarrays to narrow in

on genes affected in three peripheral nerve injury models of

neuropathic pain. The most highly regulated were involved in the

microglial complement cascade. Messenger RNAs for C1qb, C3, and C4

were upregulated in the dorsal horn of the spinal cord after injury

and were expressed only in microglia. The complement cascade

culminates in C5 and C5a receptor (C5aR) activation and formation of

the membrane attack complex (MAC). Both C5 and C5aR were upregulated

dramatically after injury. Mice lacking C5 displayed reduced

postinjury indicators of neuropathic pain, whereas animals lacking

the MAC component C6 did not. Having ruled out C3a and the MAC as

major pain effectors, the authors injected naive rats intrathecally

with the C5a anaphylatoxin. C5a increased cold pain sensitivity, and

a C5a receptor antagonist blocked this effect, consistent with a

role for C5a in neuropathic pain.