The combined efforts of neurologists, geneticists, molecular biologists, and electrophysiologists have identified genes in which rare mutations cause either extreme pain sensitivity or complete lack of pain sensation. The extreme pain syndromes include primary erythromelalgia and small fiber neuropathies that result painful extremities triggered pressure, touch, and heat. Three of these genes encode sodium ion channels called Nav1.7, Nav1.8, and Nav1.9. Additional genes associated with pain disorders are also being identified and studied. In this episode I talk with University of Oxford professor David Bennett about how research on these patients and their gene mutations have led to the development of a non-addictive and highly effective drug for severe pain that selectively blocks the Nav1.8 sodium channel. Drugs that block Nav1.7 or Nav1.9 are currently being developed. This is a remarkable example of how identification of rare genetic causes of a disorder have resulted in the development of drugs that can help reduce the suffering of everyone.

LINKS

Dr. Bennett's Oxford web page:

https://www.ndcn.ox.ac.uk/team/david-bennett

Articles related to this podcast:

https://journals.physiology.org/doi/epdf/10.1152/physrev.00052.2017

https://pmc.ncbi.nlm.nih.gov/articles/PMC4251302/pdf/practneurol-2013-000758.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC9991512/pdf/fcad037.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC5828379/pdf/jop-159-469.pdf