Lockwood, SM;
Dickenson, AH;
A combination pharmacotherapy of tapentadol and pregabalin to tackle centrally driven Osteoarthritis pain.
European Journal of Pain
10.1002/ejp.1386.
(In press).
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Abstract
BACKGROUND: Many Osteoarthritis (OA) patients report with clinical features to their pain that cannot be explained by purely peripheral mechanisms. Yet, the analgesic agents available that tackle centrally driven chronic pain often provide only partial pain relief, or have dose-limiting side effects. We explored a combination therapy of the centrally acting analgesic agents tapentadol and pregabalin, to investigate if they could be used in combination to provide superior analgesia. METHODS: Using electrophysiological single-unit recordings taken from spinal wide dynamic range (WDR) neurons, Diffuse Noxious Inhibitory Controls (DNIC) were assessed as a marker of potential changes in descending controls in a monoiodoacetate (MIA) model of OA. We investigated if a subcutaneous injection of tapentadol or pregabalin, both alone and in combination, inhibited neuronal responses and restored the expression of DNIC, quantified as a reduction in neuronal firing in the presence of a conditioning noxious stimulus. RESULTS: Tapentadol restored DNIC induced neuronal inhibition in MIA animals, while pregabalin inhibited pre-conditioned mechanically evoked neuronal responses but did not restore DNIC. Given in combination, tapentadol and pregabalin restored DNIC expression and also inhibited spinal neuronal responses. CONCLUSIONS: We propose that there is both central sensitisation and an imbalance in inhibitory and facilitatory descending controls in MIA animals. The combination therapy of tapentadol and pregabalin restored descending noradrenergic inhibitory tone, and also inhibited nociceptive transmission at the level of the spinal cord. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | A combination pharmacotherapy of tapentadol and pregabalin to tackle centrally driven Osteoarthritis pain |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/ejp.1386 |
| Publisher version: | https://doi.org/10.1002/ejp.1386 |
| Language: | English |
| Additional information: | 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. https://creativecommons.org/licenses/by/4.0/ |
| 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/10070561 |
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