Abnormal pain sensitivity is often associated with autism spectrum disorders which can affect the quality of life of those individuals. New research from two Duke University labs, Dr. Ru-Rong Ji’s Pain Signaling and Plasticity Laboratory and Dr. Yong-Hui Jiang’s autism research lab, reveals a potential mechanism underlying pain insensitivity in autism. According to an article published by Duke Today on December 1 titled, “Autism-Linked Protein Crucial for Feeling Pain,” this finding is the first to connect autism to one of the most well-studied pain receptors, TRPV1 (transient receptor potential ion channel subtype V1).
This research was published in the December 2016 issue of the journal, Neuron, in an article titled, “SHANK3 Deficiency Impairs Heat Hyperalgesia and TRPV1 Signaling in Primary Sensory Neurons.” The manuscript describes how SHANK3 (a prominent autism gene), expressed by peripheral primary sensory neurons, regulates TRPV1 function and heat hyperalgesia after inflammation and nerve injury, offering a mechanistic insight into pain dysregulation in autism. The co-first authors of this paper are Qingjian Han, PhD, Yong-Ho Kim, PhD (both with Dr. Ji’s lab), and Xiaoming Wang, PhD. Co-investigators with Duke Anesthesiology include Dr. Ji, Zhi-Jun Zhang, Di Liu, Mark Lay, Wonseok Chang, Temugin Berta and Yan Zhang.
As explained in the Duke Today article, Dr. Ji’s lab put SHANK3-dificient mice through several sensory tests which found that animals had lower sensitivity than normal mice to heat and heat-related pain, similar to that of a sunburn. Their research found 1) that not only is the SHANK3 protein present in the brain, but also in a cluster of pain-sensing neurons called the dorsal root ganglion in mice, 2) SHANK3 in the same types of cells from human donors who did not have autism, 3) that SHANK3 is expressed on the sending sides of the synapse. Dr. Ji was surprised to find that SHANK3 is expressed in the peripheral nervous system and notes that this is the first study where researchers looked for it outside of the brain – a study that could shape how effective treatments for autism are developed.
Co-expression of SHANK3 (red) and TRPV1 (green) in primary sensory neurons in mouse dorsal root ganglion in the peripheral nervous system.
Dr. Ji is the chief of pain research at Duke Anesthesiology, a distinguished professor of anesthesiology in the Duke University School of Medicine, a faculty member of Duke Anesthesiology’s Center for Translational Pain Medicine, and a member of the Duke Institute for Brain Sciences. His lab focuses on identifying molecular and cellular mechanisms that underlie the genesis of chronic pain and developing novel pain therapies that can target those mechanisms.