The potential role of serotonergic mechanisms in the spinal oxytocin-induced antinociception

Abstract The role of oxytocin (OXT) in pain modulation has been suggested. Indeed, hypothalamic paraventricular nuclei (PVN) electrical stimuli reduce the nociceptive neuronal activity ( i.e. , neuronal discharge associated with activation of Aδ- and C-fibers) of the spinal dorsal horn wide dynamic range (WDR) cells and nociceptive behavior. Furthermore, raphe magnus nuclei lesion reduces the PVN-induced antinociception, suggesting a functional interaction between the OXT and the serotoninergic system. The present study investigated in Wistar rats the potential role of spinal serotonergic mechanisms in the OXT- and PVN-induced antinociception. In long-term secondary mechanical allodynia and hyperalgesia induced by formalin or extracellular unitary recordings of the WDR cells we evaluated the role of 5-hydroxytryptamine (5-HT) effect on the OXT-induced antinociception. All drugs were given intrathecally (i.t.). OXT (1 × 10 − 5 –1 × 10 − 4  nmol) or 5-HT (1 × 10 − 3 –1 × 10 − 1  nmol) prevented the formalin-induced sensitization, an effect mimicked by PVN stimulation. Moreover, administration of OXT (1 × 10 − 5  nmol) plus 5-HT (1 × 10 − 3  nmol) at ineffective doses, produced antinociception. This effect was antagonized by: (i) d(CH 2 ) 5 [Tyr(Me) 2 ,Thr 4 ,Tyr-NH 2 9 ]OVT (oxytocin receptor antagonist; 2 × 10 − 2  nmol); or (ii) methiothepin (a non-specific 5-HT 1/2/5/6/7 receptor antagonist; 80 nmol). Similar results were obtained with PVN stimulation plus 5-HT (5 × 10 − 5  nmol). In WDR cell recordings, the PVN-induced antinociception was enhanced by i.t. 5-HT and partly blocked when the spinal cord was pre-treated with methiothepin (80 nmol). Taken together, these results suggest that serotonergic mechanisms at the spinal cord level are partly involved in the OXT-induced antinociception.