Map of human sensory neurons provides clues to chronic pain cure

RICHARDSON, Texas — Humans and animals share plenty of similarities, but a new study finds our nerve cells differ in some pretty important ways. Researchers from The University of Texas at Dallas say their investigation into the human body’s pain-sensing nerve cells are revealing clues into how scientists may be able to cure chronic pain.

Dr. Ted Price’s team analyzed how pain-sensing nerve cells (nociceptors) generate pain in the dorsal root ganglia (DRG) neurons. Their study charted the full range of messenger RNA (mRNA) strands which these cells produce.

Since mRNA are single-stranded copies of a gene that can change into proteins, study authors say their findings provide a better understanding about which genes are expressed within DRG neurons. More specifically, DRG neurons are specialized nerve cells that sit in a cluster near the base of the spine.

Animal studies may actually be hindering pain research

The research team says few groups have access to human DRG neurons, which is why animal studies are much more common when it comes to the study of pain. Despite that, the new study finds that there are key differences between species which make some pain research involving animals less applicable to people.

“This paper is the next step, clearly demonstrating the profound scale of those differences,” says Price in a university release. “An entire set of nociceptors that many people study in mice just aren’t found in humans. There are subtypes in humans that don’t exist even in nonhuman primates.”

“It’s not that we should abandon all existing nonhuman models of pain. But some are really good, while others aren’t, depending on what you want to study. When it comes to this aspect of pain, our work shows which is which.”

To categorize all of the gene activity taking place inside DRG tissue, the team used a technique called spatial transcriptomics, which is more advanced than standard single-cell RNA sequencing.

“It’s rare to have access to both the human tissue we used and to the technology,” says co-first author Dr. Diana Tavares-Ferreira. “Spatial transcriptomics allows us to overcome the large size of these neurons and to see with a degree of certainty where and how a gene is expressed in human nociceptors.”

“Our main goal was to fully characterize the whole transcriptome of human DRG neurons because so much of the work that’s been done to find new pain therapeutic targets has been in mice. Our results help clarify why those efforts struggle to produce results.”

How will this cure chronic pain?

Price says that the new study provides a much clearer picture of what each gene does inside human DRG. This includes what neuron types are present and each gene’s physiological function.

“With that knowledge, not only can anybody use our data to seek drug targets that they couldn’t have sought before, but in some cases we also don’t need to use the mice at all now. We can use the human information,” Price explains.

“We’re now able to approach developing pain therapeutics in a more specific way and to think about how chronic pain happens in people in a different way,” the lead researcher concludes. “My hope is that our findings can change the way people do research in our field. It’s a road map that we will use, and others are welcome to follow.”

The study is published in the journal Science Translational Medicine.

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