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

本研究阐明了血小板活化因子（PAF）拮抗剂在几种不同的周围神经损伤模型中对神经性疼痛的疗效，并将其纳入抗异常性痛作用的机制中。经静脉和口服给药的PAF拮抗剂对几种不同神经病变模型的小鼠具有有效的抗异常性痛作用。此外，PAF拮抗剂在小鼠炎症性疼痛模型中具有有效的抗炎和镇痛作用。这些效果是在低剂量和持久的情况下实现的。鞘内注射PAF拮抗剂和抗PAF受体的siRNA可改善异位性疼痛。总之，这些结果表明，PAF加重了外周和脊柱前觉性炎症反应，并有助于炎症性和神经性疼痛的发病机制。PAF/PAF受体系统的调控可能是未来病理性疼痛治疗创新的目标。

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.