Potential pain-releasing action of PAF antagonists in neuropathic pain animal models and the mechanisms of action

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The present study elucidated the effectiveness of platelet-activating factor (PAF) antagonists against neuropathic pain in several different models of peripheral nerve injury and inserted them into the mechanism of anti-allodynia action. PAF antagonists by intravenous and oral administration have potent anti-allodynia action in mice with several different models of neuropathies. Also, PAF antagonists have potent anti-inflammatory and analgesic action in mice inflammatory pain models. Those effects were achieved with low doses and long lasting. Intrathecal injection of the PAF antagonists and siRNA against PAF receptor ameliorated allodynia. Together, these results suggest that PAF aggravates peripheral and spinal pronociceptive inflammatory responses and contributes to the pathogenesis of inflammatory and neuropathic pain. Regulation of PAF/PAF receptor system may be targets for future innovations for pathological pain management.