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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05265806 ### Funding Statement This study was funded by the Key Technological Projects of Guangdong Province (grant number:2018B030335001). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of the University of Electronic Science and Technology of China gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors