Effects of intranasal oxytocin on thermal pain in healthy men: a randomized functional magnetic resonance imaging study.

OBJECTIVE: Intranasal oxytocin has been shown to affect human social and emotional processing, but its potential to affect pain remains elusive. This randomized, placebo-controlled, double-blind, crossover trial investigated the effect of intranasal oxytocin on the perception and processing of noxious experimental heat in 36 healthy male volunteers. METHODS: Thermal thresholds were determined according to the Quantitative Sensory Testing protocol. A functional magnetic resonance imaging experiment including intensity and unpleasantness ratings of tonic heat was used to investigate the effects of oxytocin within the brain. RESULTS: Thirty men (aged 18-50 years) were included in the study. Intranasal oxytocin had no significant effect on thermal thresholds, but significantly (t = -2.06, p = .046) reduced heat intensity ratings during functional magnetic resonance imaging. The effect on intensity ratings was small (-3.46 points on a 100-point visual analog scale [95% confidence interval {CI} = -6.86 to -0.07] and independent of temperature. No effects of oxytocin on stimulus- or temperature-related processing were found at the whole-brain level at a robust statistical threshold. A region of interest analysis indicated that oxytocin caused small but significant decreases in left (-0.045%, 95% CI = -0.087 to -0.003, t = -2.19, p = .037) and right (-0.051%, 95% CI = -0.088 to -0.014], t = -2.82, p = .008) amygdala activity across all temperatures. CONCLUSIONS: The present study provides evidence for a significant but subtle inhibitory effect of oxytocin on thermal stimulus ratings and concurrent amygdala activity. Neither of the two effects significantly depended of temperature; therefore, the hypothesis of a pain-specific effect of oxytocin could not be confirmed. TRIAL REGISTRATION: EUDRA-CT 2009-015115-40.