The drugs we've developed to help us deal with chronic pain largely focus on suppressing its symptoms, rather than eliminating its underlying causes. By studying the way pain works in injured fruit flies, scientists have for the first time uncovered evidence that its effects can be long-lasting, something they say opens up new opportunities for more effective treatments in humans.

"People don't really think of insects as feeling any kind of pain," said Associate Professor Greg Neely at the University of Sydney, Australia, who led the research. "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'."

Fruit flies often serve as models in studies of this kind because they possess far smaller and simpler genomes than other animals, which scientists can tinker with to understand different behaviors and conditions in humans. In the past, we've seen scientists get them drunk to understand why hangovers occur and study certain fruit fly proteins that could help us live longer and healthier lives.

Scientists first learned that fruit flies could experience something resembling pain back in 2003, but the evidence only alluded to short-lived discomfort. Scientists at the University of Sydney have again enlisted the winged insect in a bid to probe the mysteries of human pain, this time around producing what they say is the first genetic evidence of chronic pain that endures long after the initial injury has healed.

Brain and ventral nerve cord of an uninjured fly showing nociceptive sensory neurons can be seen in green, stained with an inhibitory neurotransmitter (red) and neuronal synaptic marker nc82 (blue) University of Sydney

"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," says Neely.

To arrive at this finding, Neely and his team damaged a nerve in one leg of a fruit fly and left it to heal. Though the acute pain had passed, the researchers found the fly's other legs had also become hyper-sensitive. Further investigation pinned the reasons for this on what the researchers describe as pain brakes, which reside in the fly's ventral nerve cord (its version of a spinal cord) and control the flow of pain signals through its body.

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

In humans, a state of hypervigilance can mean a sustained, heightened sensitivity to pain, which leads to chronic pain. This research focused on one form, known as neuropathic pain, which arises from damage to the nervous system (inflammatory pain is the other type of chronic pain). The researchers believe similar braking mechanisms might be at play when it comes to neuropathic pain humans, but in a different sort of way.

Associate Professor Greg Neely (right) and colleague Dr Thang Khuong University of Sydney

Animal's release these pain brakes as a survival mechanism in response to dangerous situations, but when the brakes are released in humans, it condemns them to sustained discomfort. Thankfully, this research opens up new possibilities around how we might be able to put them back in place.

"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," says Neely.

The research has been published in the journal Science Advances.

Source: University of Sydney