Insects Experience Chronic Pain after Serious Injury

Insects can enter a neuropathic pain-like state after nerve injury, according to a new study in fruit flies (Drosophila melanogaster).

Khuong et al offer the first genetic evidence of what causes chronic pain in Drosophila melanogaster. Image credit: Virvoreanu Laurentiu.

Khuong et al offer the first genetic evidence of what causes chronic pain in Drosophila melanogaster. Image credit: Virvoreanu Laurentiu.

Chronic pain is defined as persistent pain that continues after the original injury has healed. It comes in two forms: inflammatory pain and neuropathic pain.

The study looked at neuropathic pain, which occurs after damage to the nervous system and, in humans, is usually described as a burning or shooting pain.

“People don’t really think of insects as feeling any kind of pain,” said study senior author Dr. Greg Neely, a researcher at the University of Sydney.

“But it’s already been shown in lots of different invertebrate animals that they can sense and avoid dangerous stimuli that we perceive as painful.”

“In non-humans, we call this sense nociception, the sense that detects potentially harmful stimuli like heat, cold, or physical injury, but for simplicity we can refer to what insects experience as pain.”

“So we knew that insects could sense pain, but what we didn’t know is that an injury could lead to long lasting hypersensitivity to normally non-painful stimuli in a similar way to human patients’ experiences.”

In the study, Dr. Neely and colleagues damaged a nerve in one leg of the fly. The injury was then allowed to fully heal.

After the injury healed, the scientists found the fly’s other legs had become hypersensitive.

“After the animal is hurt once badly, they are hypersensitive and try to protect themselves for the rest of their lives. That’s kind of cool and intuitive,” Dr. Neely said.

Next, the study authors genetically dissected exactly how that works.

“The fly is receiving pain messages from its body that then go through sensory neurons to the ventral nerve cord, the fly’s version of our spinal cord. In this nerve cord are inhibitory neurons that act like a gate to allow or block pain perception based on the context,” Dr. Neely explained.

“After the injury, the injured nerve dumps all its cargo in the nerve cord and kills all the brakes, forever. Then the rest of the animal doesn’t have brakes on its pain. The pain threshold changes and now they are hypervigilant.”

“Animals need to lose the pain brakes to survive in dangerous situations but when humans lose those brakes it makes our lives miserable. We need to get the brakes back to live a comfortable and non-painful existence.”

In humans, chronic pain is presumed to develop through either peripheral sensitization or central disinhibition.

“From our unbiased genomic dissection of neuropathic pain in the fly, all our data points to central disinhibition as the critical and underlying cause for chronic neuropathic pain,” Dr. Neely said.

“Importantly now we know the critical step causing neuropathic pain in flies, mice and probably humans, is the loss of the pain brakes in the central nervous system, we are focused on making new stem cell therapies or drugs that target the underlying cause and stop pain for good.”

The study was published in the journal Science Advances.

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Thang M. Khuong et al. 2019. Nerve injury drives a heightened state of vigilance and neuropathic sensitization in Drosophila. Science Advances 5 (7): eaaw4099; doi: 10.1126/sciadv.aaw4099

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