Pain-Sensing Neurons Created From Human, Mouse Skin Cells

Chuck Bednar for redOrbit.com – Your Universe Online
Two different teams of researchers, one led by scientists from The Scripps Research Institute (TSRI) and the other involving members of the Harvard Stem Cell Institute (HSCI) have discovered ways to create the neurons that detect pain, itch and other sensations in laboratory conditions out of human and mouse skin cells.
The TSRI study, which was published online Monday in the journal Nature Neuroscience, used what the authors referred to as a simple technique to create neurons that normally reside in clusters called dorsal root ganglia (DRG) along the outer spine. Those neurons are often affected by spinal cord injuries and a neurodegenerative condition known as Friedreich’s ataxia.
According to the researchers, DRG sensory neurons extend their nerve fibers into skin, muscle and joints located throughout the body. The neurons are capable of alternately detecting gentle touch, painful contact, heat, cold, wounds, inflammation, chemical irritants, itch-inducing agents and fullness of the bowels and bladder. They also relay information about the position of the body and limbs, and have been linked to aging and autoimmune disease.
Due to the difficulties involved in culturing adult human neurons, most research relating to DRG neurons has been done in mice. However, the rodents are of limited use in understanding the human version of this “somatosensory” system, TSRI explained. The new discovery will allow this type of human neurons and their associated sensory mechanisms to be studied with relative ease in laboratory conditions, according to the study authors.
“We have found a way to produce induced sensory neurons from humans where these genes can be expressed in their ‘normal’ cellular environment,” associate professor Kristin K. Baldwin, an investigator in TSRI’s Dorris Neuroscience Center, said in a statement. “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.”
Similarly, the HSCI-led study, which included experts from Boston Children’s Hospital (BCH) and Harvard’s Department of Stem Cell and Regenerative Biology (HSCRB), was able to successfully convert mouse and human skin cells into pain-sensing neurons that responded to several different types of stimuli responsible for causing both acute and inflammatory pain.
The authors of this study, which also appeared in Wednesday’s online edition of Nature Neuroscience, said that their research could help scientists better understand the different types of pain that we experience, as well as better identify why people respond to pain in different ways and why some individuals are more or less likely to develop chronic pain. It could also result in the development of improved pain-relieving medications.
The six-year project resulted in the creation of neuronal pain receptors that respond to both the types of intense stimuli triggered by a physical injury, and the more subtle stimuli triggered by inflammation which results in pain tenderness. The researchers report that the fact the neurons can respond to both the gross and fine forms of stimulation which produce separate types of pain in humans confirm that they are functionally normal.
HSCI Executive Director Brock Reeve said that the project “exemplifies the type of long-term collaboration between academia and industry that is critical for advancing basic science and providing new ways to discover drugs,” and said that despite early struggles, the investigative team “had a dogged kind of persistence” which allowed their efforts to pay off as they discovered new transcription factors previously undetected in mice that allowed them to transform the skin cells directly into pain-sensing neurons.
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