Gene Mutation Which Prevents Carriers From Feeling Pain Discovered By Cambridge Led Team

Researchers have discovered a gene mutation which prevents the otherwise healthy carriers from sensing pain, after studying three related families with a rare genetic disorder in northern Pakistan.

The research, published in the journal Nature, provides insight into the mechanics of pain and could lead to the development of more effective pain treatments.

The carriers of the very rare genetic mutation are unable to perceive any form of pain but have otherwise completely normal sensory functions. The initial case study was a ten-year-old street performer in Pakistan with the genetic mutation. His inability to feel pain enabled him to place knives through his arms and walk on burning coals. (The young boy died before his fourteenth birthday from injures sustained after jumping off a roof.)

The scientists subsequently studied six individuals with the genetic mutation from three related families, all originating from northern Pakistan. The six relatives had not experienced pain at any time in their lives. Detailed neurological examinations revealed that there was no evidence of motor or sensory disease, and that they could perceive a number of sensations (including touch, warm and cold temperature, tickle and pressure).

As pain is a survival mechanism which enables organisms to minimise damage to tissues, they had all sustained a variety of injuries, including injuries to their lips and/or tongue from biting themselves when young.

By studying these individuals, the scientists were able to determine that a mutation in the gene SCN9A causes a loss of function in the voltage-gated sodium channel it encodes (subunit Nav1.7). Sodium channels are proteins which excite neurons, and though the precise function of Nav1.7 is unclear, as part of a sodium channel it would play a role in exciting sensory neurons.

Dr Geoffrey Woods, from the Department of Medical Genetics and the University of Cambridge Institute for Medical Research (CIMR), said, “This paper shows that rare diseases can still be of great importance, because of the insights they give into biological and developmental processes".

Dr John Wood, from University College London, said, “The work of Geoff Woods and his team has provided us with an exciting new target for pain killing drugs - potentially this is as important as the identification of the morphine receptors. It is fascinating that this same gene, when mutated to encode a hyperactive channel, has also been found to contribute to ongoing pain in some heritable human disorders”.

As individuals with mutations in the gene SCN9A are otherwise healthy, the scientists are hopeful that the development of drugs that prevent Nav1.7 from functioning could be used as new and potentially safer pain medications.

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The collaborative study, spearheaded by academics at the University of Cambridge, included researchers from a number of Pakistani and UK institutions (including University College London) and was funded in part by the Wellcome Trust.

Contact: Genevieve Maul
University of Cambridge