biorxiv.org
Oxytocin Modulation of Spinal Circuits Drives Therapeutic Benefits of Massage
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. ### Competing Interest Statement The authors have declared no competing interest. Simons Foundation, https://ror.org/01cmst727 NIH, R01NS119268, R01NS124799, U24AT011970, K99NS133476 Pew Charitable Trusts, https://ror.org/02xhk2825 Whitehall Foundation, https://ror.org/00her7k05 Craig H Neilsen Foundation Rita Allen Foundation, https://ror.org/0515k5w36 Alfred P. Sloan Foundation, https://ror.org/052csg198 New Jersey Commission on Spinal Cord Research Agence Nationale de la Recherche, ANR-18-CE16-1190 0002-01, ANR-19-CE14-0033-01 Labex ICST ANR Fondation pour la Recherche Médicale Neurodon Knut and Alice Wallenberg Foundation, https://ror.org/004hzzk67 NIA, AG055378 JSPS KAKENHI, 20K06467, 23K05612
