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Comparison of ex vivo and in vitro actions of gabapentin in superficial dorsal horn and the role of extra-spinal sites of drug action

Alles, SRA; Smith, PA; (2018) Comparison of ex vivo and in vitro actions of gabapentin in superficial dorsal horn and the role of extra-spinal sites of drug action. Neuroscience Letters , 694 pp. 148-153. 10.1016/j.neulet.2018.11.050. Green open access

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Abstract

Although gabapentin (GBP) is a first-line treatment in the management of neuropathic pain, its mechanism of action is incompletely understood. We have previously shown, in rats made neuropathic following sciatic chronic constriction injury, that IP injection of 100 mg/kg GBP decreases overall excitability of spinal cord slices obtained ex vivo. Excitability was assessed using confocal imaging to monitor the amplitude of K+- induced increases in cytoplasmic Ca2+. This decrease in excitability involved a reduction in the frequency and amplitude of spontaneous EPSC’s (sEPSC) in putative excitatory substantia gelatinosa neurons and an increase in sEPSC frequency in putative inhibitory neurons. We used have whole-cell recording to compare these ex vivo actions of GBP with its acute in vitro effects on spinal cord slices obtained from neuropathic but drug-free rats. While GBP (100μM) decreased sEPSC amplitude and frequency in excitatory neurons in vitro in a similar fashion to effects observed ex vivo, sEPSC frequency in inhibitory neurons was decreased in vitro rather than increased. Acute in vitro application of GBP also failed to decrease the overall excitability of slices from neuropathic animals as monitored by confocal Ca2+ imaging. Since spinal cord slices in vitro are disconnected from the periphery and higher brain centres, the GBP-induced increase in sEPSC frequency in inhibitory neurons previously reported and seen ex vivo must result from extra-spinal actions. It may be attributable to alterations in descending neurotrophic control of dorsal horn circuitry.

Type: Article
Title: Comparison of ex vivo and in vitro actions of gabapentin in superficial dorsal horn and the role of extra-spinal sites of drug action
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neulet.2018.11.050
Publisher version: https://doi.org/10.1016/j.neulet.2018.11.050
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Neuropathic painalpha-2-delta, Substantia gelatinosa, Descending modulation, Top down pain modulation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10063934
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