The role of peripheral vasopressin 1A and oxytocin receptors on the subcutaneous vasopressin antinociceptive effects

Background Vasopressin (AVP) seems to play a role as an antinociceptive neurohormone, but little is known about the peripheral site of action of its antinociceptive effects. Moreover, AVP can produce motor impairment that could be confused with behavioural antinociception. Finally, it is not clear which receptor is involved in the peripheral antinociceptive AVP effects. Methods In anaesthetized rats with end‐tidal CO2 monitoring, extracellular unitary recordings were performed, measuring the evoked activity mediated by Aβ‐, Aδ‐, C‐fibres and post‐discharge. Behavioural nociception and motor impairment were evaluated under subcutaneous AVP (0.1–10 μg) using formalin and rotarod tests. Selective antagonists to vasopressin (V1AR) or oxytocin receptors (OTR) were used. Additionally, vasopressin and oxytocin receptors were explored immunohistochemically in skin tissues. Results Subcutaneous AVP (1 and 10 μg/paw) induced antinociception and a transitory reduction of the end‐tidal CO2. The neuronal activity associated with Aδ‐ and C‐fibre activation was diminished, but no effect was observed on Aβ‐fibres. AVP also reduced paw flinches in the formalin test and a transitory locomotor impairment was also found. The AVP‐induced antinociception was blocked by the selective antagonist to V1AR (SR49059) or OTR (L368,899). Immunohistochemical evidence of skin VP and OT receptors is given. Conclusions Subcutaneous AVP produces antinociception and behavioural analgesia. Both V1a and OTR participate in those effects. Our findings suggest that antinociception could be produced in a local manner using a novel vasopressin receptor located in cutaneous sensorial fibres. Additionally, subcutaneous AVP also produces important systemic effects such as respiratory and locomotor impairment. Significance Our findings support that AVP produces peripheral antinociception and behavioural analgesia in a local manner; nevertheless, systemic effects are also presented. Additionally, this is the first detailed electrophysiological analysis of AVP antinociceptive action after subcutaneous administration. The results are reasonably explained by the demonstration of V1AR and OTR in cutaneous fibres.