Effect of phospholipase A2 activation on pain transmission in rat spinal dorsal horn neurons

本实验观察了磷脂酶A_2（PLA_2）激活剂蜂毒素（melittin）对胶状质（substantia gelatinosa，SG）神经元突触传递的影响。本实验采用全细胞膜片钳技术对成年大鼠脊髓片SG神经元进行记录。蜂毒肽可增加多巴胺能自发兴奋性突触后电流（sEPSC）、GABA能和甘氨酸能自发抑制性突触后电流（sIPSC）的频率和幅度。在Na^+通道阻断剂河豚毒素存在的情况下，未观察到蜂毒肽对GABA能sIPSC和sEPSC的作用，但对甘氨酸能sIPSC和sEPSC无作用。蜂毒肽对GABA能传递的作用可被谷氨酸受体拮抗剂CNQX和APV所抑制，表明蜂毒肽对GABA能传递的增强作用是通过其对兴奋性传递的易化作用介导的。PLA_2抑制 ...更多信息 抑制剂4-溴苯甲酰甲基溴抑制蜂毒肽对sEPSC和甘氨酸能sIPSC的作用。蜂毒肽对sEPSCs的作用不受环氧合酶抑制剂吲哚美辛和脂氧合酶抑制剂去甲二氢愈创木酸的影响，而去甲二氢愈创木酸抑制蜂毒肽诱导的甘氨酸能传递增强，而吲哚美辛不抑制。这些结果表明，SG内PLA_2的激活以突触前和突触后方式增强兴奋性传递是通过花生四烯酸本身的作用，而不是通过环氧合酶和脂氧合酶产生的其代谢产物。对兴奋性传递的易化作用导致增强GABA能抑制性传递。另一方面，甘氨酸能抑制性传递被甘氨酸能突触上的PLA_2激活所加强，这种作用可能是由脂氧合酶的代谢产物而不是环氧合酶介导的。结论：PLA_2激活对SG神经元兴奋性和抑制性信息传递的调节方式不同，可能在SG神经元伤害性信息传递的调节中起作用。

We examined the effect of phospholipase A_2 (PLA_2) activator melittin on synaptic transmission in substantia gelatinosa (SG ; lamina II of Rexed) neurons which play a pivotal role in regulating nociceptive transmission to the spinal dorsal horn from the periphery. The experiment was performed by applying the whole-cell patch-clamp technique to the SG neurons of adult rat spinal cord slices. Melittin increased the frequency and amplitude of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs), GABAergic and glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs). The effect of melittin on GABAergic but not glycinergic sIPSCs and sEPSCs was not seen in the presence of Na^+-channel blocker tetrodotoxin. The effect of melittin on GABAergic transmission was inhibited by glutamate-receptor antagonists, CNQX and APV, indicating that the melittin-induced enhancement of GABAergic transmission is mediated by its facilitatory effect on excitatory transmission. PLA_2 inhi … More bitor 4-bromophenacyl bromide depressed the effect of melittin on sEPSCs and glycinergic sIPSCs. The effect of melittin on sEPSCs was not affected by both cyclooxygenase inhibitor indomethacin and lipoxygenase inhibitor nordihydroguaiaretic acid, while nordihydroguaiaretic acid but not indomethacin depressed melittin-induced enhancement of glycinergic transmission. These results indicate that the activation of PLA_2 in the SG enhances excitatory transmission in a pre-and postsynaptic manner through actions of arachidonic acid itself but not its metabolites produced by cyclooxygenase and lipoxygenase. The facilitatory action on excitatory transmission results in enhancing GABAergic inhibitory transmission. On the other hand, glycinergic inhibitory transmission is potentiated by PLA_2 activation at glycinergic synapses; this action is possibly mediated by the metabolites of lipoxygenase but not cyclooxygenase. It is concluded that excitatory and inhibitory transmission in SG neurons are modulated by PLA_2 activation in a manner different from each other ; this action may play a role in regulating nociceptive transmission in the SG Less