Shank2 identifies a subset of glycinergic neurons involved in altered nociception in an autism model.
Florian Olde Heuvel, Najwa Ouali Alami, Oumayma Aousji and 15 others
PMID 37316943WHAT IT FOUND
In mice modeling a specific autism gene mutation, pain hypersensitivity stems from faulty spinal inhibition.
Loss of Shank2 weakens excitatory drive to glycinergic interneurons, preventing them from suppressing pain signals. This mechanism explains cold and chemical pain sensitivity but does not translate to human therapy.
Key findings
01Shank2-deficient mice show hypersensitivity to inflammatory pain and cold allodynia, but not heat or baseline mechanical pain.
02High Shank2 expression identifies a subpopulation of inhibitory glycinergic interneurons in the spinal cord that receive direct sensory input.
03Loss of Shank2 reduces NMDA receptor clusters on these interneurons, blunting their activation during pain and leading to over-excitation of pain-transmitting neurons.
STILL TO COME
How it was doneWhat they found
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What it does not show
The study was conducted exclusively in male mice, so findings may not apply to females. Results are specific to the Shank2 gene mutation and may not generalize to other genetic causes of autism or general ASD populations. Human data was limited to post-mortem tissue distribution and did not include functional pain testing. The study describes a mechanism in a mouse model and provides no evidence that this mechanism causes pain issues in humans or that targeting it changes clinical outcomes.
Declared interests
The authors declared no competing interests. Funding was provided by the Deutsche Forschungsgemeinschaft (German Research Foundation) and other non-US government sources.
The easy way to misread this
Do not assume this explains pain sensitivity in your patients. This is a basic science study in mice with a specific genetic mutation; it does not provide evidence for any physical therapy intervention or diagnostic tool for human autism-related pain.