Human Genetics of Pain

Inherited pain disorders are typically rare in the general population. However, in the postgenomic era, single-gene mutations for numerous human Mendelian pain disorders have been described owing to advances in sequencing technology and improvements in pain phenotyping. This article describes the history, phenotype, gene mutations, and molecular/cellular pathology of painless and painful inherited monogenic disorders. The study of these disorders has led to the identification of key genes that are needed for the normal development or function of nociceptive neurons. Genes that are covered include ATL1, ATL3, DNMT1, DST, ELP1, FLVCR1, KIF1A, NGF, NTRK1, PRDM12, RETREG1, SCN9A, SCN10A, SCN11A, SPTLC1, SPTLC2, TRPA1, WNK1, and ZFHX2. The study of some Mendelian disorders of pain sensing has the potential to lead to new classes of analgesic drugs.