Research presented at the meeting of The European Pain Federation Congress (EFIC) , held in Florence this year, covered all aspects of pain management. It was attended by 4,000 pain specialists from 75 countries. There was some interesting news.
One of the more unusual experiments reported at The EFIC was that UK researchers found that pain is less intense when people are hungry. Researchers from Liverpool University used a painful laser on the hands of people who had been fed, or who had fasted overnight. Reported pain was stronger during the sated than during the hungry state.
“Hunger and pain are basic homoeostatic drives that compete for behavioural responses when experienced together,” said Dr. Hazel Wright, one of the study authors. New research from neuroscientists at the University of Pennsylvania has found that chronic pain can be suppressed by feelings of hunger. This unique evolutionary quirk, controlled by a very small population of brain cells, could offer researchers novel new targets for pain treatments.
The research lab’s focus is generally on studying the neurological ways that hunger alters perception. “We didn’t set out having this expectation that hunger would influence pain sensation so significantly,” says Amber Alhadeff, a postdoctoral researcher on the study, “but when we saw these behaviors unfold before us, it made sense. If you’re an animal, it doesn’t matter if you have an injury, you need to be able to overcome that in order to go find the nutrients you need to survive.”
Initial studies explored the behavioral differences in mice when exposed to either acute pain or longer-term inflammatory pain, after 24 hours of food deprivation. While the effect of hunger had no impact on the animals’ sense of acute pain, there was a significant reduction in the response to inflammatory pain. “It was really striking,” Alhadeff says. “We showed that acute response to pain was perfectly intact, but inflammatory pain was suppressed to a very significant extent.”
The next step was to hone in on the area of the brain that was modulating this balance between hunger and pain. Knowing that agouti-related protein (AgRP) neurons are fundamental in activating a body’s hunger sensation, the team artificially stimulated those neurons and discovered a distinct correlation between hunger rising and chronic pain responses reducing.
Getting even more targeted, the team stimulated individual AgRP neuron subpopulations to directly hunt down the controlling brain region. It was unexpectedly discovered that an incredibly small and specific region of AgRP neurons that communicate with the parabrachial nucleus were responsible for suppressing inflammatory pain in combination with rising sensations of hunger. “The really interesting thing to my mind is that out of a brain of billions of neurons, this specific behavior is mediated by 300 or so neurons,” says J. Nicholas Betley, one of the Penn professors leading the research.
Finally, the study discovered that a specific molecule called NPY is the neurotransmitter that can modulate these inflammatory pain sensations. When NPY is blocked, hunger dissipates, and feelings of pain increase. If this neural circuit can be verified in humans and effectively manipulated it could offer an incredibly novel way to deal with chronic inflammatory pain while still maintaining a body’s sense of acute pain – important for basic survival reasons.
“We don’t want to shut off pain altogether,” Alhadeff says, “there are adaptive reasons for pain, but it would be great to be able to target just the inflammatory pain.” The researchers are excited by the potential clinical relevance of their findings. If they hold up in humans, this neural circuit offers a target for ameliorating the chronic pain that can linger after injuries, a type of pain that is currently often addressed by opioid medications, drugs that also inhibit acute pain.
Taking the next steps in this line of work, the researchers would like to map out in greater depth how the brain processes inflammatory pain, ideally identifying more targets for suppressing it. And they will continue considering how different survival behaviors integrate in the brain and how the brain processes and prioritizes them.
“We’ve initiated a new way of thinking about how behavior is prioritized,” Betley says. “It’s not that all the information is funneled up to your higher thinking centers in the brain but that there’s a hierarchy, a competition that occurs between different drives, that occurs before something like pain is even perceived.”
Who knew staying a little more hungry, rather than full might be another way to deal with chronic pain? Yet another good reason to push away from the table sooner, than later.