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[Preprint]. 2026 Mar 3:2026.01.11.698886. Originally published 2026 Jan 12. [Version 2] doi: 10.64898/2026.01.11.698886

Oxytocin Modulation of Spinal Circuits Drives Therapeutic Benefits of Massage

Manon Bohic, Paula Celeste Salamone, Wanhong Zuo, Ahmed Negm, Sasha Leilani Fulton, Shibin Du, Swathi Jayakumar, Jessica Keating, Vanessa Soubeyre, Mark Andrew Gradwell, Aman Upadhyay, Lucero Shorter, Joel Kim, Yukiko Ueno Inoue, Takayoshi Inoue, Brett Mensch, Jiang-Hong Ye, Cedric Peirs, Gaetan Poulen, Nicolas Lonjon, Florence Vachiery-Lahaye, Luc Bauchet, Emmanuel Bourinet, Hakan Olausson, Ishmail Abdus-Saboor, Yuan-Xiang Tao, Rebecca Boehme, Victoria E Abraira
PMCID: PMC12871349  PMID: 41648209

Abstract

Across social species, social touch enhances well-being and reduces pain — two seemingly distinct benefits that enhance survival. Yet where and how the nervous system integrates these functions, and whether a single mechanism could serve both, remains unknown. Here we show that massage triggers oxytocin release, which shapes both pain and touch reward at the earliest stage of central processing — the spinal cord — through a single, state-dependent circuit mechanism. We report that in humans, massage enhances well-being, effects that correlate with endogenous oxytocin release. In mice, gentle touch activates hypothalamic oxytocin neurons that project directly to the spinal dorsal horn. Genetic manipulation of spinal oxytocin circuits alters behavioral responses to both gentle touch and noxious stimuli. Spinal calcium imaging and slice electrophysiology reveal that oxytocin acts on both excitatory and inhibitory spinal neurons to sculpt the relative activity of spinal ascending systems that convey both social touch and pain to the brain. Extending these findings to humans, we show that oxytocin receptors are also expressed on spinal excitatory and inhibitory neurons, and that endogenous oxytocin during massage correlates with altered spinal touch processing. Thus, spinal oxytocin signaling provides an evolutionarily conserved mechanism for the therapeutic benefits of massage.

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