Functional Genetics Study of Human Pain Insensitivity Suggests New Avenue for Pain Treatment

A new study in Brain sheds light on how disruptions in the FAAH-OUT gene, which encodes a long non-coding RNA, causes pain insensitivity in humans. The endogenous cannabinoid system (eCBS) is involved in pain modulation, anxiety and stress responses, memory, and wound healing. Fatty acid amide hydrolase (FAAH) is an enzyme that degrades various metabolites that are part of the eCBS. A patient with a deletion in FAAH-OUT and a SNP in FAAH was found to be not only pain-insensitive but also to have reduced anxiety and fast wound healing. Through gene editing, the researchers showed that the FAAH-OUT disruption reduces expression of FAAH through increased methylation of a promoter. In addition, the deleted region contains a regulatory element that normally enhances FAAH expression. Microarray analysis of patient-derived cells unearthed a network of pathways and genes that become dysregulated due to the mutations. "Given that FAAH is a potential target for the treatment of pain, anxiety, depression, and other neurological disorders, this new understanding of the regulatory role of the FAAH-OUT gene provides a platform for the development of future gene and small molecule therapies," the authors write.