title: New Mendelian Disorders of Painlessness.
abstract: Erroneous activation of the pain-sensing system, as in chronic or neuropathic pain, represents a major health burden with insufficient treatment options. However, the study of genetic disorders rendering individuals completely unable to feel pain offers hope. All causes of congenital painlessness affect nociceptors, evolutionarily conserved specialist neurons able to sense all type of tissue damage. The discovery of new genes essential for sensing pain (SCN11A, PRDM12, and CLTCL1) has provided unexpected insights into the biological mechanisms that drive distinct stages of nociception. Drugs targeting two previously discovered painlessness genes, NGF and SCN9A, are currently in late-stage clinical trials; thus, characterization of these new painlessness genes has significant potential for the generation of new classes of analgesics.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK. Electronic address: msn27@cam.ac.uk.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Nahorski
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK. Electronic address: ycc33@cam.ac.uk.
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK. Electronic address: cw347@cam.ac.uk.
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Woods
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D033922:Clathrin Heavy Chains / Q000235:genetics; D006801:Humans; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D058748:Pain Perception / Q000502:physiology*; D010468:Perceptual Disorders / Q000235:genetics* / Q000503:physiopathology
chemical_list: C101272:CLTCL1 protein, human; D002352:Carrier Proteins; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C587499:Prdm12 protein, human; C491886:SCN11A protein, human; D033922:Clathrin Heavy Chains