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Oxytocin inhibits the membrane depolarization-induced increase in intracellular calcium in capsaicin sensitive sensory neurons: a peripheral mechanism of analgesic action

BACKGROUND: Lumbar intrathecal injection of oxytocin produces antinociception in rats and analgesia in humans. Classically, oxytocin receptors couple to stimulatory G proteins, increase inositol-3-phosphate production, and result in neuronal excitation. Most work to date has focused on a spinal site of oxytocin to excite gamma-aminobutyric acid interneurons to produce analgesia. Here we ask whether oxytocin might also affect primary sensory afferents by modulating high voltage-gated calcium channels, such as it does in the brain. METHODS: Dorsal root ganglion cells from adult rats were acutely dissociated and cultured, and changes in intracellular calcium determined by fluorescent microscopy using an indicator dye. The effects of oxytocin alone and in the presence of transient depolarization from increased extracellular KCl concentration were determined, and the pharmacology of these effects were studied. Cells from injured dorsal root ganglion cells after spinal nerve ligation were also studied. RESULTS: Oxytocin produced a concentration-dependent inhibition of the increase in intracellular calcium from membrane depolarization, an effect blocked more efficiently by oxytocin- than vasopressin-receptor selective antagonists. Oxytocin-induced inhibition was present in cells responding to capsaicin, and when internal stores of calcium were depleted with thapsigargin. Oxytocin produced similar inhibition in cells from animals with spinal nerve ligation. CONCLUSIONS: These data suggest that oxytocin produces antinociception after intrathecal delivery in part by reducing excitatory neurotransmitter release from the central terminals of nociceptors

Keywords : Adult,Affect,agonists,Analgesia,Analgesics,analogs & derivatives,Anesthesiology,Animals,antagonists & inhibitors,Brain,Calcium,Calcium Channels,Capsaicin,Cells,Cultured,cytology,Dose-Response Relationship,Drug,drug effects,Ganglia,Spinal,Hormone Antagonists,Humans,Interneurons,Ligation,Male,Membrane Potentials,metabolism,methods,Microscopy,Microscopy,Fluorescence,Microscopy,Video,Neurons,Nociceptors,Oxytocin,pharmacology,Rats,Rats,Sprague-Dawley,Receptors,Oxytocin,Sensory Receptor Cells,Sensory System Agents,Spinal Nerves,surgery,Time Factors,Universities,Vasotocin,, Inhibits,Membrane,Depolarizationinduced,Increase, back pain london

Date of Publication : 2012 Feb

Authors : Hobo S;Hayashida K;Eisenach JC;

Organisation : Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA

Journal of Publication : Anesth Analg

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/22104073

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