GENE MUTATION THAT ARE CAPABLE OF REGULATING PAIN

At least 1.5 billion people suffer from pain worldwide, and painkillers can have adverse effects like reliance and tolerance. TRPV1, a sensory neuron receptor that detects noxious stimuli including heat and the burning sensation, discovered a probable pain insensitivity mutation in the gene encoding this protein was researched Butantan Institute's Special Pain and Signaling Laboratory (LEDS) in So Paulo, Brazil.

The researchers began by exploring a genome database to compare the genetic sequences of avian and human TRPV1. Using a computational approach, they identified five avian mutations they believed to be linked to resistance to pain. Cryogenic electron microscopy showed that the five avian mutations were located in K710, an amino acid residue believed to control gating (opening and closing) of the TRPV1 channel.

According to research published in the Journal of Clinical Investigation in 2022, human gene mutations are possible but extremely uncommon. The scientists utilized the CRISPR/Cas9 gene editing method and the mutation K710N, which was discovered to lessen the receptor's response to capsaicin in cells, to examine what would occur if they were "transplanted" into animals. Lack of nociceptive behavior's and reduced neuropeptide release in mutant mice resulted in neurogenic inflammation and edoema without changing body temperature. They also displayed reduced hypersensitivity to nerve injury, restrained acute behavioral reactions to noxious stimuli, and restored baseline levels of pain hypersensitivity brought on by nerve injury.

TRPV1 has also been discovered to function as an intracellular molecular sensor that guards against tissue ischemia or cellular stress brought on by glucose. The scientists created a peptide called V1-cal that exclusively affected the K710 area and significantly reduced chronic pain.

Source:

São Paulo Research Foundation (FAPESP)

Journal reference:

He, S., et al. (2022) A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents. Journal of Clinical Investigation. doi.org/10.1172/JCI163735.