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A Mole Rat Species Is Immune to Pain from Exposure to Wasabi Spice; Key Seems to Be Rapid Evolution of Leak Channels in Nerve Cells Disrupting Transmission of Signal of Stinging Ant; Finding May Provide Insight into Solving Pain in Humans

A new report in th May 31, 2019 issue of Science provides the first evidence of a mammal -- the highveld mole-rat, a close relative of the well-known and extraordinarily long-lived naked mole rat -- being immune to pain from exposure to allyl isothiocyanate (AITC), the active ingredient of wasabi. Wasabi is a plant of the Brassicaceae family, which also includes horseradish and mustard in other genera. A paste made from wasabi’s ground rhizomes is used as a pungent condiment for sushi and other foods. The scientists who studied the highveld mole rats say that understanding how these African rodents evolved to be insensitive to this specific type of pain could point to new directions for solving pain in humans. "Mole-rats are extremely curious animals and we have been studying them at UIC for more than 20 years," said study co-author Thomas Park, PhD, Professor of Biological Sciences at the University of Illinois at Chicago (UIC) College of Liberal Arts and Sciences. "This new discovery -- that they have evolved to be insensitive to certain pain stimuli common in their environment -- is another example of the cool biological lessons to be learned from studying them." Dr. Park worked alongside scientists from the Max Delbruck Center for Molecular Medicine in Berlin and the University of Pretoria in Pretoria, South Africa, on the study. The research was conducted at UIC and in South Africa. The new Science article is titled “Rapid Molecular Evolution of Pain Insensitivity in Multiple African Rodents.” The researchers exposed the paws of eight species of mole rats to three compounds that induce a pain-like response. The three compounds were AITC, an acidic solution with a pH similar to that of lemon juice, and capsaicin, the spicy ingredient in chili peppers. The scientists monitored behaviors, such as the time an animal spent licking its paws after being exposed to a small drop of the chemicals. The scientists compared these observed behaviors with those they observed in mice when exposed to the same compounds. Following euthanasia, the scientists also extracted spinal cord tissue and nerve tissues for analysis.

Three of the mole rat species were immune to the acidic solution and two were immune to capsaicin, but the naked mole rat was the only species immune to both.

The scientists also found that the highveld mole rate was immune to exposure to the AITC compound.

"This is an awesome finding because the highveld mole rat is the only mammal known to be immune to 'wasabi pain,'" Dr. Park said. "It turns out that highveld mole rats share their tunnels, their natural environment in Africa, with a stinging ant species, the natal droptail ant. The ant's sting normally activates the same pain receptors that respond to wasabi. Over time, the highveld mole-rats evolved to become unaffected by the sting."

Dr. Park and his colleagues also analyzed genetic materials from the samples they took from the mole rats and found that the nerves of highveld mole rats had an unusually large number of tiny structures called leak channels on their surface.

"Nature and evolution solved a pain problem for the highveld mole rat. The leak channels make the nerves unable to convey messages about wasabi pain to the brain," Dr. Park said. "Instead of delivering the signal from the receptor to the brain, the leak channels divert the signal."

The researchers say that this finding is particularly interesting, as the evolutionary change for this species of mole rate occurred over a relatively short period of evolutionary time (7 million years). The related naked mole rat also developed its immunities to the acidic solution and capsaicin quickly.

"That may seem like a long time, but in evolutionary biology, 7 million years is considered to be quite rapid," Dr. Park said.

"When we find out how to add leak channels to our own pain cells, we'll have a new way of fighting pain, without the side effect of addiction from external pain killers," he said.

[Press release] [Science abstract]

[NY Times article] [Forbes article] [Popular Science article] [NewScientist article] [Independent Online article] [Cosmos article]