Pain is not perceived in the same way in people with Alzheimer’s disease

The research, published in Nature Communication, suggests that pain perception in people with Alzheimer’s disease may be impaired and questions whether changes in pain management in people with Alzheimer’s disease could improve their quality of life.

Although chronic musculoskeletal pain is common in people with Alzheimer’s disease, it remains largely untreated as it may go unreported due to the cognitive deficits associated with the disease.

In this study, the researchers sought to determine whether there is also an impairment of 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. The protein Galectin-3 has been shown to be responsible for transmitting the pain signal to the spinal cord. Upon reaching the spinal cord, it binds to another protein, TLR4, to initiate the immune response.

In this study, the researchers used an AD mouse model and gave them rheumatoid arthritis, a type of chronic inflammatory disease, via blood transfer. They observed an increase in allodynia, pain caused by a stimulus that normally does not cause pain, in response to inflammation. They also found and increased the activation of microglia – resident immune cells – in the spinal cord. They determined that these effects were regulated by TLR4.

The researchers found that mice with AD lacked TLR4 in the immune cells of their central nervous system and were therefore unable to respond to pain in the typical way because the signals were not perceived.

This led mice with AD to develop less pain related to joint inflammation and a less potent immune cell response to pain signals received by the central nervous system.

Professor Marzia Malcangio, Professor of Neuropharmacology at King’s IoPPN and lead author of the study said: “Nociceptive pain – pain that results from tissue damage – is the second most common comorbidity in people with the disease. of Alzheimer’s. Our study showed that in mice with Alzheimer’s disease, the body’s ability to process this pain is impaired due to the lack of TLR4, a protein vital for the immune response process in the central nervous system.

“These are important findings because untreated pain can contribute to psychiatric symptoms of the disease. Improving 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, PhD student at King’s IoPPN and first author of the study, said: “The results of this study have the potential to be impactful, not only in identifying galectin-3/TLR4 as a potential therapeutic target for chronic pain, but most importantly by raising awareness of the under-reported and untreated pain experienced by patients with Alzheimer’s disease.”