鞘内注射PAF受体拮抗剂对SNL大鼠痛敏和脊髓c-fos表达的影响

Effects of Intrathecal Injection with PAF Receptor Antagonists on Behavior and c-fos Expression in Spinal Cord of Rats with Spinal Nerve Ligation

目的观察鞘内注射血小板活化因子(platelet-activating factor,PAF)受体拮抗剂BN52021和BN50730对脊神经结扎(spinal nerve ligation,SNL)大鼠痛敏和脊髓原癌基因c-fos表达的影响,探讨脊髓PAF在神经病理性疼痛机制中的作用。方法雄性SD大鼠48只,鞘内置管,随机分为6组。假手术组(sham组),12只;SNL组,12只,制作SNL模型;DMSO(0.1%二甲基亚砜生理盐水,5μl)对照组、BN52021(100μg/5μl)治疗组、BN50730(100μg/5μl)治疗组和BN52021(100μg/2.5μl)+BN50730(100μg/2.5μl)治疗组,每组6只,制作SNL模型,DMSO对照组和3个治疗组鞘内注射给药,每天1次,连续给药7 d;第7天测各组大鼠机械缩爪阈值和辐射热缩爪潜伏期,放射免疫分析检测脊髓PAF含量,免疫组织化学染色检测脊髓c-fos的表达。结果SNL神经损伤诱发大鼠触觉异常痛敏和热痛敏,机械缩爪阈值和辐射热缩爪潜伏期下降(P<0.05),脊髓PAF含量升高(P<0.05),脊髓c-fos表达增强(P<0.05);BN52021和BN50730明显减轻大鼠触觉异常痛敏和热痛敏并抑制脊髓c-fos的表达增强(P<0.05)。结论内源性PAF可能参与SNL神经损伤疼痛机制,PAF的两类结合位点均介导痛觉信号传导,PAF受体拮抗剂可应用于治疗SNL神经损伤诱发的慢性疼痛。

Objective To explore the effects of intrathecal injection with PAF receptor antagonists BN52021 and BN50730 on nociceptive behavior and c-fos expression in spinal cord of rats with spinal nerve ligation（SNL）.Methods The rats with intrathecal catheters were randomly divided into 6 groups： sham,SNL,DMSO,BN52021,BN50730 and BN52021＋BN50730.SNL neuropathic pain model was established in all rats except sham group.Intrathecal injection was administered once a day for 7 days.The behavior response was observed at 7th day after injection.Immunohistochemical staining and radioimmunoassay were used to detect the expression of c-fos and PAF level in spinal cord respectively.Results SNL induced tactile allodynia and thermal hyperalgesia.The expression of c-fos and PAF level in spinal cord were increased significantly（P〈0.05） after nerve injury.BN52021 and BN50730 attenuated tactile allodynia and thermal hyperalgesia significantly（P〈0.05）,and inhibited the expression of c-fos in spinal cord（P〈0.05）.Conclusion These findings suggest a role of endogenous PAF in nociceptive transmission for SNL-induced neuropathic pain.Both intracellular and cell surface PAF binding sites are involved in nociceptive modulation in rats,and PAF receptor antagonists might be useful for treating some patients with SNL-induced neuropathic pain.