PainRelief.com Interview with:
Dr. Daniela Mauceri PH.D.
Neurobiology
Heidelberg University
Heidelberg Germany
PainRelief.com: What is the background for this study?
Response: Physiological, normal, pain prevents damage to the tissues and, in case of injury, resolves with healing. Pathological, chronic pain however, will persist after injury is mended and can manifest even in absence of causes. The transition from physiological to chronic pain is sustained by alterations of gene expression in the cell belonging to the pain circuitry such as neurons of the dorsal horn spinal cord. Epigenetic changes are important mechanisms regulating gene transcription in mammalian cells and had been previously implicated in pain chronification. A detailed understanding of which epigenetic mechanism would be critical in the establishment of chronic pain was still missing and the identity of the regulated genes still elusive.
PainRelief.com: What are the main findings?
Response: In our study we described how one particular epigenetic molecule named Histone Deacetylase 4 (HDAC4) is inactivated in the neurons of the dorsal horn spinal cord in persistent inflammatory pain. We also showed that inactivation of HDAC4 leads to increased expression of Organic Anion Transporter 1 (OAT1) and found that OAT1 is responsible for the mechanical hypersensitivity typical of chronic pain.
PainRelief.com: What should readers take away from your report?
Response: Our study suggests that finding ways to maintain HDAC4 in an active state might prevent pain chronification by blunting the upregulation of OAT1. Alternatively, blocking OAT1 activity with a pharmacological approach might also be beneficial.
PainRelief.com: What recommendations do you have for future research as a result of this work?
Response: Chronic pain is a severe pathological condition affecting a considerable part of the worldwide population. Treatments are still unsatisfactory. Our study, although performed using a mouse model of chronic inflammatory pain puts forward two potential new candidates (HDAC4, OAT1) for not only future investigations but also, importantly, for the development of future therapeutic approaches.
The research work was funded by the CRC1158 on Chronic Pain by the German Research Foundation.
Citation:
Litke, C., Hagenston, A.M., Kenkel, AK. et al. Organic anion transporter 1 is an HDAC4-regulated mediator of nociceptive hypersensitivity in mice. Nat Commun 13, 875 (2022). https://doi.org/10.1038/s41467-022-28357-x
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