title: Oxytocin inhibits the membrane depolarization-induced increase in intracellular calcium in capsaicin sensitive sensory neurons: a peripheral mechanism of analgesic action.
abstract: 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 γ-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.
authors: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors: Shotaro
authors: S
authors: Hobo
authors: Ken-ichiro
authors: K
authors: Hayashida
authors: James C
authors: JC
authors: Eisenach
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006727:Hormone Antagonists / Q000494:pharmacology; D008026:Ligation; D008297:Male; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology*; D013127:Spinal Nerves / Q000601:surgery; D013997:Time Factors; D014668:Vasotocin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000700:Analgesics; D006727:Hormone Antagonists; D018045:Receptors, Oxytocin; D018689:Sensory System Agents; C047046:atosiban; D010121:Oxytocin; D002211:Capsaicin; D002118:Calcium; D014668:Vasotocin