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

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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