Naked mole rat genes could hold the secret to pain relief without opioids

Anyone with an annoying roommate story knows that a difficult living situation can change you in many ways. Now, imagine that instead of just eating all of your food in the refrigerator, that annoying roommate could actually cause genetic changes designed to make the “future you” more tolerant of their behavior. Does it sound too good to be true? Well, this is exactly what has happened in the case of some African rodent species that live in harsh conditions characterized by acidic air, stinging insects and pungent food sources.

I am a behavioral geneticist studying how genes and the environment interact to determine the risk for chronic pain. My goal is to harness that knowledge to develop novel therapies to better treat pain without the need for opioids. Opioids are a powerful tool to treat pain, particularly acute pain, but they do not precisely target a specific pain mechanism or signal. Instead, opioids primarily act to decrease the ability of cells to transmit pain messages without actually turning off the message itself.

I was struck by this work on naked mole rats because these creatures have evolved insensitivity to very specific types of painful stimuli. This occurs as a result of subtle differences in gene activity and protein structure, rather than deletions or mutations of genes.

It is becoming more widely accepted that these types of differences in gene activity may explain individual differences in human pain sensitivity and in risk for the development of chronic pain. More importantly, if pain researchers understand these processes in these rodents and translate this work into humans, it would naturally lead to innovative methods for safe and effective pain relief.

Stinky burrows drive evolution of pain tolerance

Naked mole rats, Heterocephalus glaber, are native to East Africa and live in densely populated underground burrows. Inside these burrows, the exhaled carbon dioxide levels are so high that the air becomes so acidic that it would cause a painful burning sensation in the nose, eyes and exposed skin of most mammals.

But the naked mole rat is completely insensitive to these high acid conditions, making it extremely tolerant of all that togetherness. What’s more is that these rodents are also insensitive to capsaicin, the chemical responsible for the burning pain of chili peppers.