Effect of nortriptyline on inhibitory synaptic transmission within the substantia gelatinosa of the trigeminal subnucleus caudalis in mice
4 affiliations
- 1Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Jeonbuk National University Jeonju 54896 Korea
- 2Faculty of Odonto-Stomatology, Hue University of Medicine and Pharmacy, Hue University Hue 530000 Vietnam
- 3Department of Oral Medicine, School of Dentistry & Institute of Oral Bioscience, Jeonbuk National University Jeonju 54896 Korea
- 4Research Institute of Clinical Medicine of Jeonbuk National University - Biomedical Research Institute of Jeonbuk National University Hospital Jeonju 54907 Korea
Abstract
Nortriptyline, a tricyclic antidepressant widely used for the treatment of neuropathic pain, produces antinociceptive effects that cannot be fully accounted for by monoamine reuptake inhibition alone. Increasing evidence indicates that tricyclic antidepressants directly influence neuronal excitability and synaptic transmission within central nociceptive pathways; their actions on inhibitory neurotransmission in the trigeminal system remain incompletely characterized. In the present study, we investigated the effects of nortriptyline on inhibitory synaptic transmission in substantia gelatinosa neurons of the trigeminal subnucleus caudalis using whole-cell patch-clamp recordings in mouse brainstem slices. Nortriptyline produced a concentration-dependent increase in the frequency of spontaneous inhibitory postsynaptic currents without altering event amplitude and in an action potential–independent manner, consistent with a presynaptic mechanism. This facilitation reflected enhanced release of both GABA and glycine from presynaptic terminals. Importantly, the nortriptyline-induced enhancement of inhibitory synaptic activity persisted under Ca2+-free extracellular conditions, indicating that extracellular Ca2+ influx is not required. Collectively, these findings demonstrate that nortriptyline enhances inhibitory synaptic transmission in trigeminal substantia gelatinosa neurons primarily through presynaptic mechanisms, likely involving intracellular Ca2+ mobilization, and provide a cellular framework for its modulatory effects on orofacial nociceptive processing.
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BibTeX
@article{tran2026effect,
title = {{Effect of nortriptyline on inhibitory synaptic transmission within the substantia gelatinosa of the trigeminal subnucleus caudalis in mice}},
author = {Thi Quynh Nhu Tran and Seon Ah Park and Seon Hui Jang and Won Jung and Seong Kyu Han},
journal = {The Korean Journal of Physiology \& Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology},
year = {2026},
month = nov,
doi = {10.4196/kjpp.26.010},
url = {https://doi.org/10.4196/kjpp.26.010},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Effect of nortriptyline on inhibitory synaptic transmission within the substantia gelatinosa of the trigeminal subnucleus caudalis in mice
AU - Thi Quynh Nhu Tran
AU - Seon Ah Park
AU - Seon Hui Jang
AU - Won Jung
AU - Seong Kyu Han
PY - 2026
DA - 2026/11/01
JO - The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
DO - 10.4196/kjpp.26.010
UR - https://doi.org/10.4196/kjpp.26.010
AB - Nortriptyline, a tricyclic antidepressant widely used for the treatment of neuropathic pain, produces antinociceptive effects that cannot be fully accounted for by monoamine reuptake inhibition alone. Increasing evidence indicates that tricyclic antidepressants directly influence neuronal excitability and synaptic transmission within central nociceptive pathways; their actions on inhibitory neurotransmission in the trigeminal system remain incompletely characterized. In the present study, we investigated the effects of nortriptyline on inhibitory synaptic transmission in substantia gelatinosa neurons of the trigeminal subnucleus caudalis using whole-cell patch-clamp recordings in mouse brainstem slices. Nortriptyline produced a concentration-dependent increase in the frequency of spontaneous inhibitory postsynaptic currents without altering event amplitude and in an action potential–independent manner, consistent with a presynaptic mechanism. This facilitation reflected enhanced release of both GABA and glycine from presynaptic terminals. Importantly, the nortriptyline-induced enhancement of inhibitory synaptic activity persisted under Ca2+-free extracellular conditions, indicating that extracellular Ca2+ influx is not required. Collectively, these findings demonstrate that nortriptyline enhances inhibitory synaptic transmission in trigeminal substantia gelatinosa neurons primarily through presynaptic mechanisms, likely involving intracellular Ca2+ mobilization, and provide a cellular framework for its modulatory effects on orofacial nociceptive processing.
SN - 1226-4512
SN - 2093-3827
ER -