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Various neuropeptides modulate synaptic transmission in spinal dorsal horn lamina II (substantia gelatinosa; SG) neurons that play a pivotal role in regulating nociceptive transmission from the periphery. The SG neurons receive glutamatergic excitatory, and GABAergic and glycinergic inhibitory transmissions in a mono- and polysynaptic manner through primary-afferent fibers contained in the dorsal root. This review article introduces how several neuropeptides involved in antinociception modulate synaptic transmission in adult rat SG neurons. Nociceptin hyperpolarized the membranes and inhibited spontaneous and monosynaptically-evoked excitatory transmissions by activating opioid receptor-like1 receptors without a change in inhibitory transmission. Similar actions were produced by the activation of μ
-opioid receptors by endomorphin-1 and -2. Galanin at low concentrations presynaptically enhanced spontaneous excitatory transmission by activating galanin type-2/3 receptors whereas at high concentrations it produced a membrane hyperpolarization by galanin type-1 receptor activation; inhibitory transmission was not affected by galanin. Galanin type-2/3 but not type-1 receptor activation resulted in monosynaptically-evoked excitatory transmission inhibition. Alternatively, oxytocin produced a membrane depolarization by activating oxytocin receptors, which increased neuronal activity, resulting in the enhancement of spontaneous inhibitory transmission. Excitatory transmission was not affected by oxytocin. In conclusion, neuropeptides inhibit the excitability of SG neurons through various mechanisms, resulting in antinociception.