Chronic neuropathic pain is debilitating both physically and emotionally to the patient and to their family. This form of pain is often refractory to current pain therapies and costs this country billions of dollars a year. Current pain theory upholds that glial activation, increase expression of pro- inflammatory cytokines, and neuronal hypersensitivity all may contribute to long term potentiation of nociceptive pathways. The proposed project will utilize a spinal nerve transection animal model of neuropathic pain and mechanically lesioned mixed human neuronal and astrocytes cultures to determine the mechanism of action through which a new potentially indirect adenosine agonist produces anti-nociception (analgesia). My hypothesis is that this new potential therapeutic produces analgesia in neuropathic pain by simultaneously decreasing glial activation, pro-inflammatory cytokine expression and neuronal glutamate release. Immunohistochemistry, RT- PCR, and ELISA will be used to determine the effects of our potential indirect adenosine agonist on glial activation, pro-inflammatory cytokine expression and glutamate distribution in both an in vivo and in vitro model. This proposed study may uncover a new approach to treating neuropathic pain that employs therapeutics which target several molecular phenomenon simultaneously.
| Sweitzer, S M; Schubert, P; DeLeo, J A (2001) Propentofylline, a glial modulating agent, exhibits antiallodynic properties in a rat model of neuropathic pain. J Pharmacol Exp Ther 297:1210-7 |
| Sweitzer, S; Martin, D; DeLeo, J A (2001) Intrathecal interleukin-1 receptor antagonist in combination with soluble tumor necrosis factor receptor exhibits an anti-allodynic action in a rat model of neuropathic pain. Neuroscience 103:529-39 |
