Oxytocin Inhibits the Membrane Depolarization-Induced Increase in Intracellular Calcium in Capsaicin Sensitive Sensory Neurons: A Peripheral Mechanism of Analgesic Action
Open accessAbstract
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.
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Animal studies have shown that oxytocin can specifically reduce Aδ/C-fibre afferent signalling and ascending nociceptive input at the level of spinal cord dorsal horn neurones by engaging GABA-mediated inhibitory cellular mechanisms.
“animal studies have shown that oxytocin can specifically reduce Aδ/C‐fibre afferent signalling and ascending nociceptive input at the level of spinal cord dorsal horn neurones by engaging GABA‐mediated inhibitory cellular mechanisms 10, 11, 12, 13, 14, 29.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [29]
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- Authors
- Hobo, S., Hayashida, K.-I., & Eisenach, J. C.
- Affiliations
- Wake Forest University Health Sciences (US)
- Atrium Health Wake Forest Baptist (US)
- Corresponding author
- Eisenach, James C.
- Venue
- Anesthesia & Analgesia
- Published
- 2012-02
- Volume
- 114
- Issue
- 2
- Pages
- 442-449
- ISSN
- 0003-2999 (ISSN-L)
- PMC
- PMC3381882
- OpenAlex
- W2134949580
- Cited by
- 52
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 8 · 2017: 7 · 2016: 1 · 2015: 3 · 2014: 7 · 2013: 5 · 2012: 2
- FWCI
- 3.05
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Anesthesia & Analgesia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM048085, R37GM048085, GM 48085)
- National Center for Research Resources (M01RR007122)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- oxytocin, intracellular calcium, membrane depolarization, dorsal root ganglion neurons, primary afferent neurons, antinociception, intrathecal administration, oxytocin receptor, vasopressin receptor, spinal nerve ligation, thapsigargin, calcium store depletion, excitatory neurotransmitter release
- MeSH terms
- Analgesics, Animals, Calcium, Capsaicin, Cells, Cultured, Dose-Response Relationship, Drug, Ganglia, Spinal, Hormone Antagonists, Ligation, Male, Membrane Potentials, Microscopy, Fluorescence, Oxytocin, Sensory Receptor Cells, Spinal Nerves, Time Factors, Vasotocin, Rats, Sprague-Dawley, Receptors, Oxytocin, Sensory System Agents, Microscopy, Video, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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