GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation
Abstract
In anaesthetized rats, we tested whether the unit activity of dorsal horn neurons that receive nociceptive input is modulated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN). An electrophysiological mapping of dorsal horn neurons at L3-L4 let us choose cells responding to a receptive field located in the toes region of the left hindpaw. Dorsal horn neurons were classified according to their response properties to peripheral stimulation. Wide Dynamic Range (WDR) cells responding to electrical stimulation of the peripheral receptive field and presenting synaptic input of Adelta, Abeta, and C-fibers were studied. Suspected interneurons that are typically silent and lack peripheral receptive field responses were also analyzed. PVN electrical stimulation inhibits Adelta (-55.0+/-10.2%), C-fiber (-73.1+/-6.7%), and post-discharge (-75.0+/-8.9%) peripheral activation in WDR cells, and silent interneurons were activated. So, this last type of interneuron was called a PVN-ON cell. In WDR cells, the inhibition of peripheral responses caused by PVN stimulation was blocked by intrathecal administration of a specific oxytocin antagonist or bicuculline. However, PVN-ON cell activation was blocked by the same specific oxytocin antagonist, but not by bicuculline. Our results suggest that PVN stimulation inhibits nociceptive peripheral-evoked responses in WDR neurons by a descending oxytocinergic pathway mediated by GABAergic PVN-ON cells. We discuss our observation that the PVN electrical stimulation selectively inhibits Adelta and C-fiber activity without affecting Abeta fibers. We conclude that Adelta and C-fibers receive a presynaptic inhibition mediated by GABA.
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One mechanism of oxytocin antinociception involves engagement of GABA-mediated inhibitory circuits at superficial layers of spinal cord dorsal horn neurones, which express oxytocin receptors and receive direct projections from hypothalamic oxytocin neurones, reducing Aδ/C-fibre afferent signalling and ascending nociceptive input.
“One mechanism involves the engagement of GABA‐mediated inhibitory circuits at the superficial layers of spinal cord dorsal horn neurones, which express oxytocin receptors 7 and receive direct projections from hypothalamic oxytocin neurones 8, 9, reducing Aδ/C‐fibre afferent signalling and ascending nociceptive input 10, 11, 12, 13, 14.”
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 [10]
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 [10]
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Role of dopaminergic system in oxytocin analgesia: The missing part in a puzzle
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Guyo, F. B. (2009) · OhioLink ETD Center (Ohio Library and Information Network) · Cited by 2 · see citing works
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Exploring Nonopioid Analgesic Agents for Intrathecal Use
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Oxytocin: An Important Aspect for Designing Neuropsychiatric Drugs
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- Authors
- Rojas-Piloni, G., López-Hidalgo, M., Martínez-Lorenzana, G., Rodríguez-Jiménez, J., & Condés-Lara, M.
- Affiliations
- Universidad Nacional Autónoma de México (MX)
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 1137
- Issue
- 1
- Pages
- 69-77
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2054150356
- Cited by
- 67
- References
- 36
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 5
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, paraventricular nucleus, dorsal horn neurons, GABAergic inhibition, nociception, descending pain modulation, wide dynamic range neurons, A-delta fibers, C-fibers, presynaptic inhibition, oxytocin antagonist, bicuculline, spinal cord
- MeSH terms
- Action Potentials, Animals, Bicuculline, Brain Mapping, Electric Stimulation, gamma-Aminobutyric Acid, Nerve Fibers, Neural Inhibition, Oxytocin, Paraventricular Hypothalamic Nucleus, Rats, Wistar, GABA Antagonists, Posterior Horn Cells, Rats
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