Abstract text (incl. figure legends and references)

Question. Recent data suggest that exogenous oxytocin exerts antinociception at the trigeminal level. Although this peptide is released from the hypothalamic paraventricular nucleus (PVN), little is known about the role of endogenous oxytocinergic neurotransmission modulating trigeminal nociception. This study tested the effect of PVN stimulation on the trigeminal nociceptive responses elicited by activation of the trigeminal nerve.

Methods. In vivo electrophysiological recordings of trigeminal WDR cells and immunohistological studies were performed in rats. The animals were anesthetized with sevoflurane, assisted with mechanical ventilation, and mounted in a stereotaxic frame. A surgery to access the medullary dorsal horn was performed, and a small craniotomy was made to place a concentric stainless-steel stimulation electrode (1 MW) in the PVN. Under this condition, extracellular unitary recordings of trigeminal WDR cells with input from the first branch of the trigeminal nerve (V1) were made with quartz-Pt-W microelectrodes (4-10 MW). In addition, retrograde neuronal tracing with fluoro-gold® from the spinal trigeminal region to the PVN was assessed in search of oxytocinergic fibers.

Results. PVN electrical stimulation (6 sec, 60 Hz, 1 msec pulse duration, 300 mA) inhibited the peripheral evoked trigeminal nociceptive responses. This inhibition was reversed by a peptide OTR antagonist given spinally (dOVT, d(CH₂)₅[Tyr(Me)²,Thr⁴,Tyr-NH₂⁹]OVT). Furthermore, the retrograde labeling showed that direct oxytocinergic projections from trigeminal nucleus caudalis to PVN exist.

Conclusion. Coupled with previous reports showing that exogenous oxytocin administration at the trigeminal level inhibited the periorbital nociceptive responses via OTR, our data strongly support the notion that PVN via oxytocinergic transmission inhibits trigeminal nociception, suggesting that enhancement of oxytocinergic transmission could be used as a potential therapy to treat headaches.