One epigenetic factor as well as one organic anion transporter (OAT1), whose function in the nervous system was previously unknown, contributed to the development of chronic pain. Using mouse experiments, the researchers discovered that the OAT1 transporter regulates pain sensitivity in the spinal cord. The aim of their research is to develop new approaches for treatment.
Normal physiological pain prevents tissue damage and resolves with healing. Chronic pathological pain is inherited even if the injury has healed, according to Daniela Mauceri, a research group working in the Neurobiology department at the Institute of Medicine. Chronic pain is characterized by altering gene expression, which regulates how information from a gene is processed into a protein, or RNA molecules. This occurs particularly when cells such as neurons in the dorsal horn are affected. The sensory spectrum is the central nervous system of
The researchers have identified an epigenetic factor Histone Deacetylase 4 (HDAC4) that is a key contributor to the gene expression of neurons in the dorsal horn. In mouse experiments, they found that long-lasting pain triggered the export and thus inactivation of HDAC4 from the nucleus within each cell. Chronic pain-related reactions in the mice were reduced.
In collaboration with Prof. Dr Rohini Kuner, who leads a research group at the Institute of Pharmacology in Heidelberg, the Dr Mauceris team examined the key ingredients for the transition to chronic pain. They discovered that the organic Anion Transporter 1 (OAT1), an integrated human transporter, is responsible for the transition to chronic pain. This could, according to Dr Mauceri, lead a new therapeutic path for managing chronic pain.
Probenecid, an OAT1 blocker, was administered directly into the spinal cord with pain pumps to the mice. One particular finding was that Probenecid provided relief even after chronic pain was already present. The researchers believe their findings will further develop therapy strategies for pain if confirmed in future clinical trials. Dr Mauceri: OAT1 inhibitors, which can be administered directly into the spinal cord using pain pumps, may be helpful to evaluate this approach.