Actions of oxytocin on rat spinal dorsal horn lamina II neurons - cellular mechanisms for antinociception

Abstract

Although there is much evidence showing that a posterior pituitary hormone oxytocin is involved in antinociception in the spinal dorsal horn, this action has not been yet examined fully. We examined the effects of oxytocin on (glutamatergic) excitatory and (GABAergic and glycinergic) inhibi tory transmissions in spinal lamina II (substantia gelatinosa ; SG) neurons which play a pivotal role in modulating nociceptive transmission to the CNS from the periphery. The blind whole-cell patch-clamp technique was applied to the SG neurons in the spinal cord slices of adult male rats. In of the neurons examined, oxytocin superfused for min produced an inward current at − mV without a change in spontaneous excitatory transmission. Monosynaptically-evoked primary-afferent A-fiber and C-fiber excitatory transmissions were also unaffected by oxytocin. The oxytocin current was resistant to a voltage-gated Na +-channel blocker tetrodotoxin (TTX), indicating a direct action of oxytocin which is not accompanied by an increase in neuronal activities. The oxytocin response was mimicked by an oxytocin-receptor agonist [Thr ,Gly ]-oxytocin (TGOT) and disappeared in the presence of an oxytocin-receptor antagonist [d(CH) ,Tyr(Me) , Thr ,Orn ,des-Gly-NH ]-vasotocin (dVOT). The oxytocin current was inhibited by a phospholipase C inhibitor U-and an IP-induced Ca +-release inhibitor-aminoethoxydiphenyl borate. On the other hand, a protein kinase C inhibitor chelerythrine, a Ca +-induced Ca +-release inhibitor dantrolene and membrane-permeable dibutyryl cyclic-AMP did not affect the oxytocin activity. Current-voltage relationship for the oxytocin current reversed at negative potentials more than the equilibrium potential for K + or around mV. The oxytocin current was depressed in peak amplitude in high-K + , low-Na + or Ba +-containing Krebs solution. GABAergic and glycinergic spontaneous inhibitory postsynaptic currents were increased in frequency by oxytocin in a manner sensitive to TTX. These activities were mimicked by TGOT and inhibited by dVOT. It is concluded that oxytocin produces a membrane depolarization, probably due to Na +-permeability increase and/or K +-permeability decrease, being possibly mediated by