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Autism-linked protein crucial for feeling pain

Thursday, December 1, 2016
By Kelly Rae Chi @DukeResearch
Autism linked protein

Sensory problems are common to autism spectrum disorders. Some individuals with autism may injure themselves repetitively -- for example, pulling their hair or banging their heads -- because they’re less sensitive to pain than other people.

New research points to a potential mechanism underlying pain insensitivity in autism. The study, conducted by two teams at Duke University and appearing online Dec. 1 in the journal Neuron, is the first to connect autism to one of the most well-studied pain molecules, called TRPV1 (transient receptor potential ion channel subtype V1), which is a receptor for the main spicy component of chili peppers.

“Not enough research has been done on the mechanisms driving sensory problems in autism, but it’s important because sensory processing probably affects to some degree how the brain develops,” said co-author Yong-hui Jiang, M.D., Ph.D., associate professor of pediatrics and neurobiology at Duke. Jiang collaborated with Ru-Rong Ji, Ph.D., professor of anesthesiology and neurobiology and chief of pain research in Duke University School of Medicine’s Department of Anesthesiology. 

In a study published earlier this year, Jiang and other collaborators at Duke described a mouse model of autism in which they deleted a prominent autism gene called SHANK3, which is mutated in 1 percent of people with the disorder. These mice show several features of autism, including social deficits and excessive self-grooming.

That study did not examine pain. But about 70 percent of individuals with autism or a related disorder called Phelan-McDermid syndrome who have mutations in SHANK3 are known to have sensory processing problems, according to Jiang, who treats children with autism at Duke’s Children Hospital & Health Center.

In the new study, Ji’s group put SHANK3-deficient mice through a battery of sensory tests, finding that the animals had lower sensitivity than normal mice to heat and heat-related pain -- akin to the soreness a person feels after a sunburn.

It turns out that the SHANK3 protein is normally present not only in the brain, but also in a cluster of pain-sensing neurons called the dorsal root ganglion in mice. The group also found SHANK3 in the same types of cells from human donors who did not have autism.

“This was a big surprise that SHANK3 is expressed in the peripheral nervous system, but before this study, no one had ever looked for it outside of the brain,” Ji said.

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