Alzheimer’s disease patients may not feel pain in the same way as other people, a new study has suggested.
The research from King’s College London says this is due to the lack of a protein called TLR4 in the central nervous system.
The team behind the investigation said the finding could open the way to better pain management strategies, potentially improving the quality of life for people with Alzheimer’s disease.
While chronic musculoskeletal pain is common in individuals with Alzheimer’s, it remains largely untreated as it can go unreported due to the cognitive deficits attached to the disease.
But in this study, a team from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London, sought to explore whether there is also an alteration in the body’s response to pain by the nervous system in people with Alzheimer’s.
Using a mouse model mimicking Alzheimer’s disease, the researchers found that unlike in healthy mice, pain signals are not passed on in the same way. In healthy mice, they are transmitted from the point of origin to the central nervous system to initiate an immune response.
This is brought about by a carbohydrate binding protein called Galectin-3 which is responsible for relaying pain signals to the spinal cord.
There it binds with the TLR4 protein to initiate the immune response.
Professor Marzia Malcangio
In this study, the researchers gave the Alzheimer’s disease mice rheumatoid arthritis, a type of chronic inflammatory disease, through blood transfer.
They observed an increase in allodynia – defined as pain caused by a stimulus that doesn’t normally provoke discomfort – as a response to the inflammation. They also found an increased activation of a microglia – resident immune cells – in the spinal cord.
The researchers determined that these effects were regulated by TLR4.
The team found that the mice with Alzheimer’s disease lacked TLR4 in the immune cells of their central nervous system and were therefore unable to respond to pain in the typical way as the signals were not being perceived.
This resulted in the mice with Alzheimer’s developing less joint inflammation related soreness, and a less powerful immune cell response to the pain signals received by the central nervous system.
Marzia Malcangio, professor of meuropharmacology at King’s IoPPN and 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 the open access journal Nature Communications, was funded by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement.