Recent Research: Altered Pain Perception in Alzheimer’s Disease Patients

A recent investigation conducted by King’s College London has discovered that pain signals are interpreted differently in a mouse model for Alzheimer’s Disease (AD), due to the absence of the TLR4 protein in the immune cells within the central nervous system. This revelation, suggesting a shift in pain perception in AD, may incite a reevaluation of pain control and treatment measures for AD patients, potentially enhancing their living conditions.

Fresh results from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London indicate deviations in how pain signals are interpreted in a mouse model replicating Alzheimer’s Disease (AD), in contrast with healthy mice.

Published in Nature Communications, the study proposes that the perception of pain might be changed in individuals afflicted by Alzheimer’s Disease. This raises the issue of whether modifying pain control methods for Alzheimer’s patients could enhance their living standards.

Chronic musculoskeletal pain is frequently found in AD patients, but it often goes unmanaged due to the cognitive impairment linked with the disease, which can hinder reporting of the pain.

In this research, the investigators aimed to examine if there is also a modification in the body’s pain response by the nervous system in people with AD.

In healthy mice, pain signals are relayed from the source to the central nervous system to activate an immune response. The Galectin-3 protein has been shown to facilitate pain signal transfer to the spinal cord. Upon reaching the spinal cord, it binds to the TLR4 protein, thereby triggering the immune response.

In this study, the researchers induced rheumatoid arthritis, a chronic inflammatory condition, in an AD mouse model via blood transfer. They noticed an escalation in allodynia – pain from a stimulus which does not typically induce pain – as a reaction to the inflammation. They also observed increased activation of microglia, the resident immune cells in the spinal cord. They ascertained that TLR4 regulated these effects.

The researchers found that the AD mice lacked TLR4 in the immune cells of their central nervous system, making them unable to respond to pain as usual because the signals weren’t being registered.

This resulted in less joint inflammation-related pain in the AD mice, and a weaker immune cell response to the pain signals received by the central nervous system.

Professor Marzia Malcangio, Professor of Neuropharmacology at King’s IoPPN and the senior author of the study, stated, “Nociceptive pain – pain resulting from tissue damage – is the second most common comorbidity in individuals with Alzheimer’s disease. Our study shows that in mice with Alzheimer’s, the capacity to process pain is changed due to the absence of TLR4; a protein crucial to the immune response process in the central nervous system.

“These findings are significant because untreated pain can augment the psychiatric symptoms of the disease. Enhancing our knowledge in this domain, with additional research, could lead to more efficient treatments and ultimately improve individuals’ living conditions.”

George Sideris-Lampretsas, a PhD student at King’s IoPPN and the first author of the study, said, “The results of this study have the potential to make a significant impact, not only by identifying Galectin-3/TLR4 as a potential therapeutic target for chronic pain, but most importantly by increasing awareness of the underreported and untreated pain experienced by AD patients.”

The study was made possible thanks to financial support from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement.

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More about Alzheimer’s Disease pain perception

• King’s College London
• Alzheimer’s Disease
• Nature Communications
• European Union’s Horizon 2020 Research and Innovation Programme