Reprogrammed human and mouse cells offer way to identify new painkilling drugs.
Nerve cells that transmit pain, itch and other sensations to the brain have been made in the lab for the first time. Researchers say that the cells will be useful for developing new painkillers and anti-itch remedies, as well as understanding why some people experience unexplained extreme pain and itching.
“The short take-home message would be ‘pain and itch in a dish’, and we think that’s very important,” says Kristin Baldwin, a stem-cell scientist at the Scripps Research Institute in La Jolla, California, whose team converted mouse and human cells called fibroblasts into neurons that detect sensations such as pain, itch or temperature1. In a second paper2, a separate team took a similar approach to making pain-sensing cells. Both efforts were published on 24 November in Nature Neuroscience.
Peripheral sensory neurons, as these cells are called, produce specialized ‘receptor’ proteins that detect chemical and physical stimuli and convey them to the brain. The receptor that a cell makes determines its properties — some pain-sensing cells respond to chilli oil, for example, and others respond to different pain-causing chemicals. Mutations in the genes encoding these receptors can cause some people to experience chronic pain or, in rare cases, to become impervious to pain.
To create these cells in the lab, independent teams led by Baldwin and by Clifford Woolf, a neuroscientist at Boston Children’s Hospital in Massachusetts, identified combinations of proteins that — when expressed in fibroblasts — transformed them into sensory neurons after several days. Baldwin's team identified neurons that make receptors that detect sensations including pain, itch, and temperature, whereas Woolf’s team looked only at pain-detecting cells. Both teams generated cells that resembled neurons in shape and fired in response to capsaicin, which gives chilli peppers their kick, and mustard oil.
Both teams say that pain cells ‘in a dish’ could speed the search for new painkillers, as they could be used in screening drugs for their ability to block or alter the activity of these cells. “The number of people who take analgesics is very large, and there’s a pretty big medical need among people who have untreatable pain during chemotherapy,” says Baldwin. The anti-malarial drug chloroquine causes some people to itch — especially people of African ancestry — and studying itch cells made from their fibroblasts could help to explain why, she adds.
It will be important to make sure that the cells respond to stimuli similarly to bona fide sensory cells, says John Wood, a neuroscientist at University College London, and to determine how they communicate with immune cells and the rest of the nervous system, which both have roles in pain. “This is important work,” he says. “Nociceptive [pain-sensing] neurons play a key role in almost all acute and chronic pain conditions, and a better understanding of their biology should produce new analgesic drug targets.”
Blanchard, J. W. et al. Nature Neurosci. http://dx.doi.org/10.1038/nn.3887 (2014).
Wainger, B. J. et al. Nature Neurosci. http://dx.doi.org/10.1038/nn.3886 (2014).
Related links in Nature Research
Rat helps pinpoint pain molecule 2012-Jan-22
The itch without the pain 2009-Aug-06
Chilli opens the door to targeted pain relief 2007-Oct-04
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Callaway, E. Pain and itch neurons grown in a dish. Nature (2014). https://doi.org/10.1038/nature.2014.16401