Subcutaneous Oxytocin Injection Reduces Heat Pain: A randomized-controlled trial

Oxytocin 1 is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local. In human studies, intravenous OT has reduced visceral pain and subcutaneous injection of OT has reduced postsurgical pain. However, the local effects of subcutaneous OT on experimental pain have not been studied. We conducted a two-session crossover study during which healthy adults received a subcutaneous injection of synthetic OT (4mcg/2ml) or saline placebo (isotonic saline 2ml), in a randomized and double-blinded manner. 18 participants completed full study procedures. We hypothesized that 10 min after injection, OT would reduce measures of acute mechanical pain, pressure pain, and heat pain perception. Subcutaneous OT significantly reduced ratings of heat pain intensity and unpleasantness (both p < 0.01), but did not alter mechanical pain, pressure pain, or heat pain threshold (all p > 0.05). Changes in heat pain were observed only on the injected arm and not on the contralateral arm, confirming a localized mechanism. These findings confirm the ability of OT in or near the skin to modulate nociceptive processes in cutaneous tissues in human adults, opening exciting avenues for further mechanistic research as well as potential clinical applications for acute pain.The study purpose, targeted condition, study design, and primary and secondary outcomes were pre-registered in ClinicalTrials.gov (NCT05326776: “Peripheral Oxytocin and Touch (POPP)”). Perspective This randomized-controlled trial showed that a subcutaneous injection of oxytocin can reduce perception of heat pain tested with a thermode. Oxytocin did not alter mechanical or pressure pain, or thresholds for perceiving heat pain. These findings are relevant to scientists and clinicians seeking non-addictive local drug treatments for pain.