RT Journal Article
SR Electronic
T1 Spinal Glia and Proinflammatory Cytokines Mediate Mirror-Image Neuropathic Pain in Rats
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1026
OP 1040
DO 10.1523/JNEUROSCI.23-03-01026.2003
VO 23
IS 3
A1 Erin D. Milligan
A1 Carin Twining
A1 Marucia Chacur
A1 Joseph Biedenkapp
A1 Kevin O'Connor
A1 Stephen Poole
A1 Kevin Tracey
A1 David Martin
A1 Steven F. Maier
A1 Linda R. Watkins
YR 2003
UL http://www.jneurosci.org/content/23/3/1026.abstract
AB Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes. Allodynia refers to pain in response to light touch/pressure stimuli, which normally are perceived as innocuous. Mirror-image allodynia arises from the healthy body region contralateral to the actual site of trauma/inflammation. Virtually nothing is known about the mechanisms underlying such pain. A recently developed animal model of inflammatory neuropathy reliably produces mirror-image allodynia, thus allowing this pain phenomenon to be analyzed. In this sciatic inflammatory neuropathy (SIN) model, decreased response threshold to tactile stimuli (mechanical allodynia) develops in rats after microinjection of immune activators around one healthy sciatic nerve at mid-thigh level. Low level immune activation produces unilateral allodynia ipsilateral to the site of sciatic inflammation; more intense immune activation produces bilateral (ipsilateral + mirror image) allodynia. The present studies demonstrate that both ipsilateral and mirror-image SIN-induced allodynias are (1) reversed by intrathecal (peri-spinal) delivery of fluorocitrate, a glial metabolic inhibitor; (2) prevented and reversed by intrathecal CNI-1493, an inhibitor of p38 mitogen-activated kinases implicated in proinflammatory cytokine production and signaling; and (3) prevented or reversed by intrathecal proinflammatory cytokine antagonists specific for interleukin-1, tumor necrosis factor, or interleukin-6. Reversal of ipsilateral and mirror-image allodynias was rapid and complete even when SIN was maintained constantly for 2 weeks before proinflammatory cytokine antagonist administration. These results provide the first evidence that ipsilateral and mirror-image inflammatory neuropathy pain are created both acutely and chronically through glial and proinflammatory cytokine actions.