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

Optimal health depends critically on maintenance of an evolutionarily ancient circadian clock that ticks within all cells of the body and brain. Discovery of the genes that encode the core proteins of the molecular clock have revealed how the clock works and, importantly, how the clock influences health and resilience. Joseph Takahashi discovered the gene for CLOCK which is one of four proteins that control circadian rhythms. In this episode I talk with Joe about his discoveries concerning how the molecular clock functions, how the clock influences energy metabolism, the consequences of disruption of the clock for health, and how we can improve our circadian rhythms by, for example, daily time-restricted eating.

LINKS

Takahashi laboratory

https://labs.utsouthwestern.edu/takahashi-lab

How the cellular circadian clock works

https://pmc.ncbi.nlm.nih.gov/articles/PMC10631358/pdf/nihms-1930368.pdf

Daily time-restricted eating and circadian rhythms

https://www-annualreviews-org.proxy1.library.jhu.edu/docserver/fulltext/10.1146/annurev-nutr-112525-011241/annurev-nutr-112525-011241.pdf?expires=1779798437&id=id&accname=ar-223467&checksum=908E9889190B85725CE892E63BB5413C

In this episode I talk with MIT neuroscientist Ev Fedorenko about the neural networks that process language in the human brain, the relationships between the processing of language and thought, evolutionary perspectives on thinking versus communicating, and artificial intelligence systems as tools for advancing understanding of the neurobiology of language. To understand the neural networks of language and their relationships with networks for cognition, perception, and motor systems the Fedorenko lab uses fMRI, intracranial recordings, EEG, behavioral experiments, and computational modeling. Her research includes studies of development of the language network, and the effects aging, aphasias and other neurological disorders on the networks.

LINKS

Dr. Fedorenko's laboratory:

https://www.evlab.mit.edu/

Recent review and perspective articles:

https://www.nature.com/articles/s41586-024-07522-w

https://www.annualreviews.org/docserver/fulltext/neuro/47/1/annurev-neuro-120623-101142.pdf?expires=1778850274&id=id&accname=guest&checksum=846F655794ACA01CB4739ABEA17B4B1C

https://www.nature.com/articles/s41583-024-00802-4