Erythermalgia: molecular basis for an inherited pain syndrome.
Inherited erythermalgia (also termed erythromelalgia) is characterized by severe pain in the limbs in response to mild thermal stimuli or exercise. Its molecular basis has, until recently, been enigmatic. Studies of families with autosomal dominant erythermalgia have now demonstrated mutations in sodium channel Na(v)1.7, which is selectively expressed within nociceptive dorsal root ganglion and sympathetic ganglion neurons. Shifts in activation and deactivation, and enhanced responses to small stimuli in mutant channels, decrease the threshold for single impulses and high-frequency trains of impulses in pain-sensing neurons. Erythermalgia, the first inherited painful neuropathy to be understood at a molecular level, is a model disease that could hold lessons for other painful conditions and for the development of rational, mechanism-based treatments for pain.
Waxman
Stephen G
SG
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA. stephen.waxman@yale.edu
Dib-Hajj
Sulayman
S
D000595:Amino Acid Sequence; D004916:Erythromelalgia / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000235:genetics*; D010641:Phenotype; D016415:Sequence Alignment; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism
D015222:Sodium Channels