Newborn analgesia mediated by oxytocin during delivery
- 1 INMED/INSERM U901, Université de la Méditerranée, Marseille, France
- 2 Department of Audiology, Université Claude Bernard Lyon I, Lyon, France
- 3 Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland
- 4 Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Center of Russian Academy of Sciences, Kazan, Russia
- 5 Spinal laboratory SISSA - IMFR, Udine, Italy
The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth.
Keywords: GABA, neonate, oxytocin, pain
Citation: Mazzuca M, Minlebaev M, Shakirzyanova A, Tyzio R, Taccola G, Janackova S, Gataullina S, Ben-Ari Y, Giniatullin R and Khazipov R (2011) Newborn analgesia mediated by oxytocin during delivery. Front. Cell. Neurosci. 5:3. doi:10.3389/fncel.2011.00003
Received: 31 January 2011;
Accepted: 31 March 2011;
Published online: 12 April 2011.
Copyright: © 2011 Mazzuca, Minlebaev, Shakirzyanova, Tyzio, Taccola, Janackova, Gataullina, Ben-Ari, Giniatullin and Khazipov. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.
*Correspondence: Rustem Khazipov, INMED/INSERM U901, 163 Route de Luminy, 13273 Marseille, France. e-mail: firstname.lastname@example.org