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

我们研究了磷脂酶A_2 （PLA_2）激活剂melittin对明胶质神经元突触传递的影响，明胶质神经元在调节伤害知觉从外周向脊髓背角的传递中起关键作用。采用全细胞膜片钳技术对成年大鼠脊髓切片SG神经元进行了实验。蜂毒素增加了谷氨酸能自发兴奋性突触后电流（sEPSCs）、gaba能自发抑制性突触后电流（sIPSCs）的频率和幅度。在Na^+通道阻滞剂河豚毒素存在的情况下，蜂毒素对gaba能而不是甘氨酸能的sIPSCs和sEPSCs的影响没有被观察到。谷氨酸受体拮抗剂、CNQX和APV均能抑制蜂毒素对gabaergy传递的影响，表明蜂毒素对gabaergy传递的增强作用是通过其对兴奋性传递的促进作用介导的。4-溴苯酰溴抑制蜂毒素对sEPSCs和甘氨酸能型sIPSCs的作用。蜂毒素对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，去甲二氢愈创木酸而非吲哚美辛抑制蜂毒素诱导的甘氨酸能传递增强。这些结果表明，PLA_2在SG中的活化通过花生四烯酸本身的作用，而不是通过其代谢产物环加氧酶和脂加氧酶的作用，在突触前和突触后增强兴奋性传递。对兴奋性传递的促进作用导致gaba能抑制传递增强。另一方面，PLA_2在甘氨酸能突触的激活增强了甘氨酸能抑制传递；这种作用可能是由脂氧合酶代谢物介导的，而不是由环氧合酶介导的。综上所述，PLA_2活化对SG神经元的兴奋性和抑制性传递的调节方式不同；这一作用可能在调节SG Less的伤害性传递中起作用

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