Oxytocin Enhances Pleasantness and Neural Responses to CT-fiber-mediated Social Touch Via Increased Peripheral Concentrations

Social touch is pleasurable and thus constitutes a key component of human social relationships. Intranasal administration of the neuropeptide oxytocin can facilitate the pleasantness of social touch although it is unclear whether it acts specifically on responses to C-touch or other types of cutaneous afferent fibers. Additionally, it is unclear whether effects of intranasal oxytocin are mediated via its direct entry into the brain or indirectly by increased peripheral concentrations. In a randomized controlled design, we therefore investigated effects of intranasally and orally (only increases peripheral concentrations) administered oxytocin on behavioral and neural responses to social touch targeting either C-touch (gentle-stroking touch) or other- (medium pressure massage) types of cutaneous receptors. Although both types of touch were perceived as pleasant, intranasal and oral oxytocin only, and equivalently, enhanced pleasantness ratings and neural responses in reward and touch processing regions to gentle-stroking touch. Plasma oxytocin concentrations also significantly predicted pleasantness ratings and were associated with brain reward responses. Together, our findings provide evidence that exogenously administered oxytocin primarily modulates behavioral and neural responses to C-touch fiber mediated social touch and suggest that it acts via peripheral-mediated routes. Clinical Trial Registration ID #: NCT05265806.