The processing of pain signals is different in a mouse model of Alzheimer’s disease (AD) compared to healthy mice, according to a recent study from King’s College London’s Institute of Psychiatry, Psychology and Neuroscience (IoPPN). The study, which was published in Nature Communications, hypothesizes that people with Alzheimer’s disease may experience pain differently, and explores how how people with AD manage their pain may affect their quality of life. Quality can be improved. While chronic musculoskeletal pain is common among individuals with AD, it is largely undiagnosed because it may go unreported due to the cognitive deficits associated with the disease.
In this study, the researchers sought to find out whether there are also changes in the body’s response to pain by the nervous system in people with AD. In healthy mice, pain signals are transmitted from the point of origin to the central nervous system to initiate an immune response. It has been demonstrated that the protein galectin-3 is responsible for pain signal transmission to the spinal cord. Upon reaching the spinal cord, it binds to another protein, TLR4, to initiate an immune response.
In this study, researchers used models of AD mice and gave them rheumatoid arthritis, a type of chronic inflammatory disease, through blood transfusions. They observed an increase in allodynia, as a response to inflammation, pain caused by a stimulus that does not normally provoke pain. They also found and increased activation of microglia – the resident immune cells – in the spinal cord. They determined that these effects were controlled by TLR4.
The researchers found that the immune cells of the central nervous system of mice with AD lacked TLR4 and were therefore unable to respond to pain in a normal way because the signals were not being interpreted. This resulted in mice with AD developing less joint inflammation-related pain, and a less potent immune cell response to pain signals received by the central nervous system.
Professor Margia Malcangio, Professor of Neuropharmacology at King’s IoPPN and senior author of the study, said, “Nociceptive pain – pain that is the result of tissue damage – is the second most prevalent comorbidity in individuals with Alzheimer’s disease. Our study showed that, in those with Alzheimer’s, In mice, a lack of TLR4 alters the body’s ability to process that pain; this protein is important for the immune response process in the central nervous system. These are important findings, as untreated pain can contribute to psychotic symptoms. disease. Increasing our understanding of this area, along with more research, could lead to more effective treatments and ultimately improve people’s quality of life.”
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“The results of this study not only identify galectin-3/TLR4 as a potential therapeutic target for chronic pain, but have the potential to impact ” But most importantly, to raise awareness of the underdiagnosed and untreated pain experienced by AD patients.”











