Patel, R;
Kucharczyk, M;
Montagut-Bordas, C;
Lockwood, S;
Dickenson, AH;
(2019)
Neuropathy following spinal nerve injury shares features with the irritable nociceptor phenotype: a back-translational study of oxcarbazepine.
European Journal of Pain
, 23
(1)
pp. 183-197.
10.1002/ejp.1300.
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Abstract
BACKGROUND: The term 'irritable nociceptor' was coined to describe neuropathic patients characterised by evoked hypersensitivity and preservation of primary afferent fibres. Oxcarbazepine is largely ineffectual in an overall patient population but has clear efficacy in a sub-group with the irritable nociceptor profile. We examine whether neuropathy in rats induced by spinal nerve injury shares overlapping pharmacological sensitives with the irritable nociceptor phenotype using drugs that target sodium channels. METHODS: In vivo electrophysiology was performed in anaesthetised spinal nerve ligated (SNL) and sham-operated rats to record from wide dynamic range (WDR) neurones in the ventral posterolateral thalamus (VPL) and dorsal horn. RESULTS: In neuropathic rats, spontaneous activity in the VPL was substantially attenuated by spinal lidocaine, an effect that was absent in sham rats. The former measure was in part dependent on ongoing peripheral activity as intraplantar lidocaine also reduced aberrant spontaneous thalamic firing. Systemic oxcarbazepine had no effect on wind-up of dorsal horn neurones in sham and SNL rats. However, in SNL rats, oxcarbazepine markedly inhibited punctate mechanical, dynamic brush and cold-evoked neuronal responses in the VPL and dorsal horn, with minimal effects on heat-evoked responses. In addition, oxcarbazepine inhibited spontaneous activity in the VPL. Intraplantar injection of the active metabolite licarbazepine replicated the effects of systemic oxcarbazepine supporting a peripheral locus of action. CONCLUSIONS: We provide evidence that ongoing activity in primary afferent fibres drives spontaneous thalamic firing after spinal nerve injury, and that oxcarbazepine through a peripheral mechanism exhibits modality-selective inhibitory effects on sensory neuronal processing. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Neuropathy following spinal nerve injury shares features with the irritable nociceptor phenotype: a back-translational study of oxcarbazepine |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ejp.1300 |
| Publisher version: | https://doi.org/10.1002/ejp.1300 |
| Language: | English |
| Additional information: | Copyright © 2018 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC® This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | In vivo electrophysiology, anticonvulsant, dorsal horn, licarbazepine, neuropathic pain, oxcarbazepine, sodium channels, spinal nerve ligation, ventral posterolateral thalamus, wide dynamic range |
| 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 Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10054685 |
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