Researchers at UC Santa Barbara identified a pain pathway in fruit flies that reduces the sensation of pain from heat. The researchers discovered that just a single neuron on each side of the animal’s brain controls the response. The molecule is also responsible for suppressing this sensation in adult flies but has the opposite role in fly larvae.

The findings are published in Current Biology in an article titled, “Alleviation of thermal nociception depends on heat-sensitive neurons and a TRP channel in the brain.”

“Acute avoidance of dangerous temperatures is critical for animals to prevent or minimize injury,” wrote the researchers. “Therefore, surface receptors have evolved to endow neurons with the capacity to detect noxious heat so that animals can initiate escape behaviors. Animals including humans have evolved intrinsic pain-suppressing systems to attenuate nociception under some circumstances. Here, using Drosophila melanogaster, we uncovered a new mechanism through which thermal nociception is suppressed. We identified a single descending neuron in each brain hemisphere, which is the center for suppression of thermal nociception.”

The brain of a fruit fly has about a million-fold fewer neurons than our own. “Yet we didn’t anticipate that a single pair of neurons would have such an important role in pain suppression,” explained senior author Craig Montell, PhD, the Duggan professor and distinguished professor of molecular, cellular, and developmental biology.

“We call them ‘Epione,’ or Epi neurons, for the Greek goddess of soothing pain,” said first author Jiangqu Liu, PhD, a postdoctoral fellow in the Montell lab.

The researchers focused on nociception in response to heat. Liu, Montell, and their co-authors used the DNA segments that control the expression of 35 different neuropeptide genes to drive expression of a protein that activates neurons.

Out of the 35 different groups of neurons, one stood out. These neurons produce the neuropeptide AstC, which is related to a mammalian compound that contributes to pain suppression in humans.

The researchers then expressed the gene coding for a light-sensitive channel in this group of neurons. Stimulating these neurons reduced the flies’ tendency to jump off the hot plate.

The authors then used the section of DNA that controls expression of AstC to instead control a gene for green fluorescent protein. Now they could finally see which neurons were activating. That’s when they discovered that triggering just a single neuron on each side of the brain (the Epi neurons) suppressed the nociceptive response.

“This is the first time, to my knowledge, that a TRP channel is found to sense noxious heat not to induce a nociceptive response, but to suppress it,” Montell added.

The team plans to further investigate the pathways involved in this anti-nociception response. Their work raises the question as to whether a thermally-activated TRP channel might suppress nociception in mammals as well.

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