Newborn Analgesia Mediated by Oxytocin during Delivery
Open Access
- 1 January 2011
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cellular Neuroscience
Abstract
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 two days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in two days-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 choride 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.This publication has 68 references indexed in Scilit:
- Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trialThe Lancet, 2010
- Chloride regulation in the pain pathwayBrain Research Reviews, 2009
- Neonatal injury alters adult pain sensitivity by increasing opioid tone in the periaqueductal grayFrontiers in Behavioral Neuroscience, 2009
- Na+,K+,2Cl− Cotransport and Intracellular Chloride Regulation in Rat Primary Sensory Neurons: Thermodynamic and Kinetic AspectsJournal of Neurophysiology, 2008
- NKCC1 Phosphorylation Stimulates Neurite Growth of Injured Adult Sensory NeuronsJournal of Neuroscience, 2007
- Oxytocin increases trust in humansNature, 2005
- Human and Murine Phenotypes Associated with Defects in Cation-Chloride CotransportAnnual Review of Physiology, 2002
- Development of thermal nociception in ratsPain, 1996
- Pain and Its Effects in the Human Neonate and FetusThe New England Journal of Medicine, 1987
- Feto‐Maternal Plasma Oxytocin Levels in Normal and Anencephalic PregnanciesActa Obstetricia et Gynecologica Scandinavica, 1983