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