Oxytocin (OT) has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, OT receptors (OTRs) in the spinal dorsal horn participate in a selective inhibition of the neuronal activity mediated by Aδ and C fibers but not Aβ fibers. This study shows that OTRs are expressed in the terminal nerve endings and are able to inhibit nociceptive neuronal firing. Indeed, local peripheral OT blocked the first sensorial activity of Aδ and C fibers recorded in the spinal cord neurons. Furthermore, using the formalin behavioral nociceptive test, we demonstrated that only ipsilateral OTR activation inhibits pain behavior. Our data are reinforced by the fact that the OTR protein is expressed in the sciatic nerve. Consistent with this, immunofluorescence of primary afferent fibers suggest that OTRs could be located in nociceptive-specific terminals of the skin. Taken together, our results suggest that OTRs could be found in nociceptive terminals and that on activation they are able to inhibit nociceptive input.