ORIGINAL ARTICLE The role of peripheral vasopressin 1A and oxytocin receptors on the subcutaneous vasopressin antinociceptive effects A. Manzano-Garc  ıa, A. Gonz alez-Hern andez, I.A. Tello-Garc  ıa, G. Mart  ınez-Lorenzana, M. Cond es-Lara Departamento de Neurobiolog  ıa del Desarrollo y Neurofisiolog  ıa, Instituto de Neurobiolog  ıa, Universidad Nacional Aut onoma de M exico, Quer etaro, M exico Correspondence Miguel Cond es-Lara E-mail: condes@unam.mx Funding sources and conflict of interest disclosure This work was sponsored by grant (to M. Cond es-Lara) PAPIIT-UNAM (Grant No. IN200415) and (to A. Gonz alez-Hern andez) PAPIIT-UNAM (Grant No. IA203117). A. Manzano-Garc  ıa is a doctoral student from Programa de Doctorado en Ciencias Biom edicas, Universidad Nacional Aut onoma de M exico (UNAM) and received fellowship (597467) from CONACYT. I.A. Tello-Garc  ıa also is a doctoral student form Programa de Doctorado en Ciencias Biom edicas, UNAM and received fellowship (414165) from CONACYT. Conflicts of interest disclosures The authors have no conflicts of interest to declare Accepted for publication 23 September 2017 doi:10.1002/ejp.1134 Abstract 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 CO 2 monitoring, extracellular unitary recordings were performed, measuring the evoked activity mediated by Ab-, Ad-, C-fibres and post-discharge. Behavioural nociception and motor impairment were evaluated under subcutaneous AVP (0.1–10 lg) using formalin and rotarod tests. Selective antagonists to vasopressin (V 1A R) or oxytocin receptors (OTR) were used. Additionally, vasopressin and oxytocin receptors were explored immunohistochemically in skin tissues. Results: Subcutaneous AVP (1 and 10 lg/paw) induced antinociception and a transitory reduction of the end-tidal CO 2 . The neuronal activity associated with Ad- and C-fibre activation was diminished, but no effect was observed on Ab-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 V 1A R (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 V 1A R and OTR in cutaneous fibres. 1. Introduction Arginine-vasopressin (AVP), a neurohypophysial hormone well known for its effects on water homeostasis and blood pressure regulation, has been implied as a potential peptide modulating nocicep- tion. In rodents, intracerebroventricular (Kordower © 2017 European Pain Federation - EFIC â Eur J Pain  (2017) – 1