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The medullary dorsal horn (MDH or Sp5c/C1 region) plays a key role modulating the nociceptive input arriving from craniofacial structures. Some reports suggest that oxytocin could play a role modulating the nociceptive input at the MDH level, but no study has properly tested this hypothesis. Using an electrophysiological and pharmacological approach, the present study aimed to determine the effect of oxytocin on the nociceptive signaling in the MDH and the receptor involved. In sevoflurane, anesthetized rats, we performed electrophysiological unitary recordings of second order neurons at the MDH region responding to peripheral nociceptive-evoked responses of the first branch (V1; ophthalmic) of the trigeminal nerve. Under this condition, we constructed dose-response curves analyzing the effect of local spinal oxytocin (0.2–20 nmol) on MDH nociceptive neuronal firing. Furthermore, we tested the role of oxytocin receptors (OTR) or vasopressin V1A receptors (V1AR) involved in the oxytocin effects. Oxytocin dose-dependently inhibits the peripheral-evoked activity in nociceptive MDH neurotransmission. This inhibition is associated with a blockade of neuronal activity of Aδ- and C-fibers. Since this antinociception was abolished by pretreatment (in the MDH) with the potent and selective OTR antagonist (L-368,899; 20 nmol) and remained unaffected after the V1AR antagonist (SR49059; 20 nmol or 200 nmol), the role of OTR is implied. This electrophysiological study demonstrates that oxytocin inhibits the peripheral-evoked neuronal activity at MDH, through OTR activation. Thus, OTR may represent a new potential drug target to treat craniofacial nociceptive dysfunction in the MDH.Medullary dorsal horn (MDH) is involved in craniofacial nociception.Oxytocin administration at MDH inhibits the peripheral-evoked nociception.Blockade of oxytocin receptors (OTR) inhibits the oxytocin-induced antinociception.The effect of oxytocin on MDH neurotransmission is not mediated by V1A receptors.Relevance of oxytocinergic neurotransmission at spinal trigeminal level is suggested.