FROUNT-mediated pain control of Anti-alcoholism drug disulfiram

Abstract

Astrocytes are important regulators of CNS functions, including neurotransmission, and play an important role in the etiology of pain. Recently, we have shown that the alcoholism drug disulfiram (DSF) exerts its anticancer effects by directly binding to FROUNT, a protein that promotes signaling through chemokine receptor (CCR)2 and CCR5 expressed on macrophages, and by inhibiting FROUNT function (Nature Communications. 2020: 609). In addition, it has been reported that chemokine receptors including CCR2 and CCR5 are involved in pain regulation. The purpose of this study was to verify the analgesic effects of DSF on various pain models. Formalin model mice were used to evaluate acute nociceptive pain, reserpine model mice were used to evaluate chronic nociceptive pain, and sciatic nerve partial ligation model mice were used to evaluate neuropathic pain. DSF showed analgesic effects on these pain models. In addition, the reduction of pain threshold in reserpine model mice was not observed in FROUNT-deficient mice. And we found that FROUNT-positive cells co-localized with GFAP-positive astrocytes in the dorsal horn of the spinal cord. These results suggest that DSF, an existing treatment for alcohol dependence, may become a new pain treatment with a new mechanism.