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RARβ agonist drug (C286) demonstrates efficacy in a pre-clinical neuropathic pain model restoring multiple pathways via DNA repair mechanisms

Research output: Contribution to journalArticlepeer-review

Maria B. Goncalves, Julien Moehlin, Earl Clarke, John Grist, Carl Hobbs, Antony M. Carr, Julian Jack, Marco Antonio Mendoza-Parra, Jonathan P.T. Corcoran

Original languageEnglish
Pages (from-to)554-566
Number of pages13
Early online date17 Sep 2019
Accepted/In press12 Sep 2019
E-pub ahead of print17 Sep 2019
Published25 Oct 2019


King's Authors


Neuropathic pain (NP) is associated with profound gene expression alterations within the nociceptive system. DNA mechanisms, such as epigenetic remodelling and repair pathways have been implicated in NP. Here we have used a rat model of peripheral nerve injury to study the effect of a recently developed RARβ agonist, C286, currently under clinical research, in NP. A four week treatment initiated two days after the injury normalised pain sensation. Genome-wide and pathway enrichment analysis showed that multiple mechanisms persistently altered in the spinal cord were restored to preinjury levels by the agonist. Concomitant upregulation of DNA repair proteins, ATM and BRCA1, the latter being required for C286 mediated pain modulation, suggest that early DNA repair may be important to prevent phenotypic epigenetic imprints in NP. Thus, C286 is a promising drug candidate for neuropathic pain and DNA repair mechanisms may be useful therapeutic targets to explore.

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