The Analgesic Effect Of Oxytocin In Humans:A Double-Blinded Placebo Controlled Cross-Over Study Using Laser-Evoked Potentials

Oxytocin is a neuropeptide regulating social-affiliative and reproductive behavior in mammals. Despite robust preclinical evidence for exogenous oxytocin's antinociceptive effects and mechanisms of action, human studies have produced mixed results regarding oxytocin's analgesic role and are yet to show a specific modulation of neural processes involved in pain perception. Here we investigated the analgesic effects of 40IU of intranasal oxytocin in 13 healthy male volunteers using a double-blinded, placebo-controlled, cross-over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ- and C-fiber nerve endings in the epidermis, while recording ensuing laser evoked potentials (LEPs). We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1, N2 and P2 components. We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 (but not of P2) LEPs, and increased the latency of the N2 component. Importantly, for the first time, this study reports an association between the analgesic effect of oxytocin (reduction in subjective pain ratings) and the oxytocin-induced modulation of cortical activity following noxious stimulation (attenuation of the N2 LEP). These effects indicate that oxytocin modulates neural processes contributing to pain perception. This study presents preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C-fibre nociceptive afferent signaling at the spinal level and provide further specificity to evidence from humans that oxytocin may be modulating pain experience by modulating activity in cortical areas involved in pain processing. This article is protected by copyright. All rights reserved.