CIRM-Funded Scripps Team Replicates Pain in a Lab Dish; Seeks New Treatments for Chronic Sufferers

Pain hurts but it also protects. Thanks to nerve cells called sensory neurons, which weave their nerve fibers throughout our skin and other tissues, we are alerted to dangerous events like touching a hot plate or even to the sense of having a full bladder.

However, trauma such as a spinal cord injury or diseases like HIV and diabetes can damage sensory neurons and cause chronic pain that debilitates rather than protects those affected. Sadly, conventional pain treatments are usually not effective for the stinging, burning, tingling and numbness associated with this type of pain. Clearly, new innovations are needed.

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These induced sensory neurons could be useful in the testing of potential new therapies for pain, itch and related conditions. Credit: Baldwin Lab, The Scripps Research Institute

Last week, a CIRM-funded research team from The Scripps Research Institute, reported in Nature Neuroscience that they developed a technique, which induces human skin cells to transform into sensory neurons in a petri dish. Up until now, the field mostly relied on mouse studies due to the difficulty of collecting and growing human sensory neurons in the lab. This may explain the lack of success in clinical trials for treating chronic pain. As co-lead author Joel Blanchard, a PhD candidate in Kristin Baldwin’s laboratory, stated in the institute’s press release:

“Mouse models don’t represent the full diversity of the human response. [With these human sensory neurons] we can start to understand how individuals respond uniquely to pain, cold, itch and so on.”

Kevin Eade, research associate, and Joel Blanchard, graduate student, co-lead authors of the report  Credit: Cindy Brauer, The Scripps Research Institute

Kevin Eade, research associate, and Joel Blanchard, graduate student, co-lead authors of the report. Credit: Cindy Brauer, The Scripps Research Institute

To generate the nerve cells, the Baldwin research team inserted, into human skin cells, a combination of genes known to produce proteins that are key controllers of sensory neuron function. The resulting cells had the appearance of sensory neurons and responded appropriately when exposed to heat in the form of the active ingredient in chili peppers as well as activating a cold response when exposed to menthol. Adding more confidence to these results, an independent research team from the Harvard Stem Cell Institute reported in the same Nature Neuroscience   issue and in a press release that they too had successfully generated human sensory neurons from skin cells.

This direct reprogramming of one cell type directly into another is a variant of the induced pluripotent stem cell (iPS) technique in which a cell, often skin, is first reprogrammed into an embryonic stem cell-like state and then coaxed to form into virtually any cell type of the body.

Now that the Baldwin lab has nailed down the recipe for making human sensory neurons, they now can seek out treatments to bring relief to chronic pain sufferers. Dr. Baldwin looks forward to this future work:

Kristin Baldwin, Associate Professor Department of Molecular and Cellular Neuroscience. Credit: The Scripps Research Institute

Kristin Baldwin
Associate Professor
Credit: The Scripps Research Institute

“This method is rapid, robust and scalable. Therefore we hope that these induced sensory neurons will allow our group and others to identify new compounds that block pain and itch and to better understand and treat neurodegenerative disease and spinal cord injury.”

Watch the short video below to hear from a pioneer of direct reprogramming of nerve cells, CIRM grantee Marius Wernig of Stanford University:

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