Massage Engages Spinal Oxytocin Circuits to Reduce Pain and Enhance Well-Being

Context determines how the nervous system interprets sensory information to guide adaptive behavior. Nowhere is this more consequential than in the somatosensory system where the same touch can signal threat from a predator or safety from a caregiver, injury during attack or comfort during healing. Oxytocin, a neuropeptide released across a broad range of social interactions, is well positioned to convey social context to somatosensory circuits, but at what stage of processing does this convergence occur and through what mechanism? Here we show that affiliative touch triggers oxytocin release at the earliest stage of sensory processing, the spinal cord, shaping both pain relief and touch reward through a single, state-dependent circuit that is conserved from mice to humans. In humans, massage drives endogenous oxytocin release, enhanced pain relief and well-being. Modeling this in mice shows that social touch activates hypothalamic oxytocin neurons that project to the spinal cord, where oxytocin signaling is both necessary and sufficient for pain suppression and touch reward. Moreover, spinal calcium imaging and slice electrophysiology demonstrate that oxytocin acts on both excitatory and inhibitory spinal neurons to differentially modulate the relative activity of spinal ascending systems that convey both pain and social touch to the brain. We find that this circuit architecture is conserved in humans, as oxytocin receptors are similarly expressed on spinal excitatory and inhibitory neurons. Massage-induced oxytocin release in humans correlates with slowed somatosensory processing within the spinal cord in response to aversive stimuli and reduced negative affect. Thus, spinal oxytocin circuits provide an evolutionarily conserved mechanism through which affiliative touch reduces pain and enhances well-being, linking the earliest stage of sensory processing to the social bonds on which survival depends.