Background & Aims
In addition to well-known roles in social behavior, the neuropeptide oxytocin (OT) can reduce pain, and may mediate pleasant effects of gentle touch. While centrally administered OT can reduce pain, its peripheral effects are less explored. In rodents, OT shows local antinociceptive effects in skin terminal axons, and in humans, subcutaneous OT injection reduces postoperative pain. However, its local, peripheral effects of OT on experimental pain and touch have not been studied. Here we test the local effects of subcutaneous injection of OT in humans on gentle brushing and experimental pain, hypothesizing reductions in pain and increases in brushing pleasantness. In addition, previous studies have shown associations between blood plasma OT concentrations and lower ratings of chronic pain, as well as higher tolerance of experimental pain. We therefore conducted preliminary investigations into the associations between endogenous OT and gentle touch, as well as experimental pain stimuli.
Methods
Eighteen healthy adults (mean age = 28.2; 13 female) enrolled in two-session crossover study; at each session, participants received subcutaneous synthetic OT or saline placebo in a double-blind, randomized manner. Procedures at both sessions were identical, including eligibility confirmation, questionnaires, pregnancy tests, baseline serum assays, and heart rate monitoring. Individual heat pain calibration was performed. Then, affective touch and pain tasks were conducted, before and after subcutaneous injection of oxytocin or saline placebo into the left dorsal forearm. Affective touch included fast and slow gentle brushing. Pain tasks included mechanical pain threshold (MPT), temporal summation, pressure pain threshold (PPT), and heat pain threshold (HPT), as well as intensity and (un)pleasantness ratings of extended heat pain from a thermode.
Results
Subcutaneous OT injection did not alter mechanical pain threshold, temporal summation, pressure pain, or heat pain threshold (p > 0.05). However, OT significantly reduced ratings of heat pain intensity and unpleasantness (p < 0.01).
At baseline, exploratory correlations found a significant negative correlation between endogenous serum OT level and perceived slow and fast brushing intensity (p < 0.05) and a significant positive correlation between endogenous serum OT level and PPT (p < 0.05). No significant correlations were found for brushing pleasantness, MPT, or HPT measures.
Conclusions
These findings confirm the ability of OT in or near the skin to modulate acute pain perception in healthy adults, opening many exciting possibilities for clinical research. OT may directly influence nociception at the local level, likely through its interactions with skin receptors and TRPV1 channels, which have a prominent role in heat pain perception. Furthermore, our results shed light on the complex relationship between endogenous OT and sensory perception, providing valuable insight into the multifaceted role of OT in modulating tactile and pain experience. Our findings confirm that OT may be a valuable measure to collect in in studies of acute and chronic pain. Further investigation is needed to fully understand its mechanisms and therapeutic potential.
References
1)Walker, S.C., et al., C-tactile afferents: Cutaneous mediators of oxytocin release during affiliative tactile interactions? Neuropeptides, 2017. 64: p. 27-38.
2)Mekhael, A.A., et al., Evaluating the efficacy of oxytocin for pain management: An updated systematic review and meta-analysis of randomized clinical trials and observational studies. Can J Pain, 2023. 7(1): p. 2191114.
3)González-Hernández, A., et al., Peripheral oxytocin receptors inhibit the nociceptive input signal to spinal dorsal horn wide-dynamic-range neurons. Pain, 2017. 158(11): p. 2117-2128.
4)Grewen KM, Light KC, Mechlin B, et al. Ethnicity is associated with alterations in oxytocin relationships to pain sensitivity in women. Ethn Health. 2008;13:219–241.
Presenting Author
Benedetta Albinni
Poster Authors
Benedetta Albinni
PhD
University of California San Diego
Lead Author
Marisa Zimmerman BS
UCSD
Lead Author
Jacob Ross BS
UCSD
Lead Author
Leyla Ozdoyuran
UCSD
Lead Author
Vincent Alasha BA
UCSD
Lead Author
Ramamurthy Chitteti PhD
UCSD
Lead Author
Alex Jinich-Diamant MA
UCSD
Lead Author
Nathaniel M. Schuster
MD
UCSD
Lead Author
Engy Said MD
UCSD
Lead Author
Laura Case PhD
UCSD
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)