Altered Pain Perception in Alzheimer’s Disease Could Lead to Improved Pain Management

Alzheimer’s Disease (AD) may alter the perception of pain due to a lack of a protein called TLR4 in the central nervous system, according to new research from King’s College London. This discovery may lead to better pain management strategies for AD patients, potentially improving their quality of life.

In individuals with Alzheimer’s Disease, chronic musculoskeletal pain often goes untreated, largely because it goes unreported due to cognitive deficits associated with AD. Researchers at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London have discovered that this might also be due to alterations in how pain signals are processed in AD.

Using a mouse model mimicking Alzheimer’s Disease, the researchers found that, unlike in healthy mice, pain signals are not transmitted the same way. In healthy mice, pain signals from the point of origin are sent to the central nervous system, initiating an immune response. This is facilitated by the protein Galectin-3, which transmits pain signals to the spinal cord. There, it binds with another protein, TLR4, to initiate the immune response.

However, the study showed that mice with Alzheimer’s Disease lacked TLR4 in the immune cells of their central nervous system, and thus did not respond to pain in the normal way because the signals were not being perceived. Consequently, these mice developed less joint inflammation-related pain and had a weaker immune cell response to pain signals.

Professor Marzia Malcangio, the study’s senior author, said, “Nociceptive pain – pain which is the result of tissue damage – is the second most prevalent comorbidity in individuals with Alzheimer’s disease. Our study has shown that, in mice with Alzheimer’s, the body’s ability to process that pain is altered due to the lack of TLR4; a protein vital to the immune response process in the central nervous system. These are important findings, as untreated pain can contribute to the psychiatric symptoms of the disease. Increasing our understanding of this area could, with more research, lead to more effective treatments and ultimately improve people’s quality of life.”

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

The study, published in Nature Communications, was funded by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement.