Insects feel chronic pain too

Scientists have known insects experience something like pain since 2003, but research from the University of Sydney has now shown that insects also experience chronic pain that lasts long after an initial injury has healed. The study has been published in the journal Science Advances.

“People don’t really think of insects as feeling any kind of pain,” said Associate Professor Greg Neely, who led the new study. “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’.”

Chronic pain is defined as persistent pain that continues after the original injury has healed, and comes in two forms: inflammatory pain and neuropathic pain. The Sydney researchers focused on neuropathic pain, which occurs after damage to the nervous system and, in humans, is usually described as a burning or shooting pain.

The study saw Assoc Prof Neely and lead author Dr Thang Khuong damage a nerve in one leg of a fruit fly, which was then allowed to fully heal. After the injury healed, they 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,” said Assoc Prof Neely.

“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.”

Next, the team 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,” Assoc Prof Neely said. “In this nerve cord are inhibitory neurons that act like a ‘gate’ to allow or block pain perception based on the context.

“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.”

Brain and ventral nerve cord (resembling the spinal cord in human) of an uninjured fly showing nociceptive sensory neurons (green), stained with anti-GABA, an inhibitory neurotransmitter (red) and neuronal synaptic marker nc82 (blue).

The study thus offers the first genetic evidence of what causes chronic pain in fruit flies, and there is good evidence that similar changes also drive chronic pain in humans, which is presumed to develop through either peripheral sensitisation 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,” Assoc Prof Neely said.

Ongoing research into these mechanisms could lead to the development of treatments that target the cause and not just the symptoms of chronic pain. As noted by Assoc Prof Neely, “If we can develop drugs or new stem cell therapies that can target and repair the underlying cause, instead of the symptoms, this might help a lot of people.

“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.”

Top image credit: ©stock.adobe.com/au/Studiotouch

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