Inflammation Linked To Chronic Pain: Study

The study, published in the current issue of the Journal of Neuroscience, shows how inflammation in mice increases NR2B proteins – proteins that facilitate nerve cell communication – and imprint a painful response in brain even after the stimulus is removed. "What we're interested in uncovering are the molecular mechanisms that can turn early pain into persistent pain," says Professor Min Zhuo of physiology, EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health and lead author of the study. "We believe that the body's inflammatory response helps to etch the initial pain into our memory."

Normally when a mouse or a person experiences a painful event, receptors in the injury site send an electrical impulse up the spine and to the brain. The signal triggers receptors called glutamate AMPA and kainate, which flare up initially but do not directly alter the physiology of the cells. When the painful event also triggers inflammation, the nerves send extra information to the normally dormant NR2B receptors – receptors that receive messages and then produce physiological effects in the cell.

In the study, researchers injected a chemical irritant into the hind paws of mice, causing inflammation. They then tracked brain activity in the anterior cingulate cortex (ACC) – a region of the brain associated with pain and other functions such as decision-making and emotion. In tests performed one hour, six hours and one day after injection, they found that NR2B protein levels had increased over time. Previous research had already established a link between the protein and chronic pain. In an earlier study, Zhuo demonstrated that mice initially genetically enhanced with NR2B to boost memory and learning abilities also became acutely aware of minor pain for long periods of time. "Persistent pain caused by injury, learning and memory share the same common molecular mechanisms," Zhuo says. "By identifying these mechanisms we can greatly facilitate the treatment of chronic pain."

Zhuo hopes the findings will one day be used to create therapeutic solutions to conditions such as allodynia – a condition where even a gentle touch produces pain. Currently, pain-blocking drugs also target other brain activity – not just NR2B receptors – and can also block acute pain that acts as a body's warning system.

"It's essential that therapies don't block the body's entire pain system as pain often plays a valuable role," Zhuo says. "For instance, acute and immediate pain often tells us to remove ourselves from harm such as accidentally touching a hot plate. The key is to find a way to develop drugs that target only persistent pain thereby improving the patient's quality of living."

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The research was funded by the Canadian Institutes of Health Research, the National Institutes of Health, the EJLB-CIHR Michael Smith Chair in Neurosciences and Mental Health, and the Canada Research Chair program.