LONDON — A groundbreaking study from King’s College London’s Institute of Psychiatry, Psychology & Neuroscience sheds new light on how Alzheimer’s Disease affects pain perception, potentially paving the way for improved patient care. The study explores the mysterious realm of pain in Alzheimer’s patients. Traditional understanding suggests that people with Alzheimer’s may experience pain differently, and this study provides compelling evidence to that effect.
Chronic musculoskeletal pain, a type of pain affecting muscles and bones, is common among individuals with Alzheimer’s, yet it often goes untreated. The cognitive deficits associated with Alzheimer’s can make it difficult for patients to communicate their pain, leaving it unaddressed. In this study, researchers discovered a critical pathway that facilitates communication between sensory neurons and microglia (the immune cells in the spinal cord) under conditions of inflammatory arthritis pain. This interaction is pivotal in how pain is perceived and processed.
Microglia are not just passive observers; they actively shape the body’s response to pain through specific molecular cues. For instance, the research highlights the pro-nociceptive (pain-enhancing) effects of the protein Galectin-3 (Gal-3) in normal conditions. In a healthy body, pain signals travel from the point of injury to the central nervous system, where they trigger an immune response. This process involves Gal-3, which helps transmit pain signals to the spinal cord, where they bind to another protein, TLR4, to kickstart the immune response.
However, this effect is absent in conditions where the TLR4 protein is knocked out, underscoring the protein’s importance in pain processing.
Observations In Mice
Study authors utilized a mouse model mimicking the disease to delve into this issue. After inducing rheumatoid arthritis, a chronic inflammatory disease, through blood transfer in some mice, they observed differences in how pain signals are processed in the mice compared to healthy ones. They observed an increase in allodynia, a type of pain caused by a stimulus that typically does not provoke pain, as a response to the inflammation. Additionally, they found heightened activation of microglia — effects which were determined to be regulated by TLR4.
Researchers found these mice lacked TLR4 in the immune cells of their central nervous system, leading to a different pain response. The study observed less joint inflammation-related pain and a weaker immune response in these mice.
Another fascinating aspect of the study is the discovery that Gal-3 is released by nociceptive neurons in the spinal cord, and this release triggers microglia to adopt a TLR4-dependent profile, crucial for processing pain signals. This release of Gal-3 is a response to increased activity in the nervous system due to pain, suggesting a highly dynamic and responsive pain processing system.
Implications for Alzheimer’s Patients
Professor Marzia Malcangio, a senior author of the study, highlights the significance of these findings. “Nociceptive pain – pain which is the result of tissue damage – is the second most prevalent comorbidity in individuals with Alzheimer’s disease,” she says in a statement. “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.”
This alteration in pain processing could contribute to the psychiatric symptoms of Alzheimer’s, underscoring the need for better pain management in these patients. As untreated pain can exacerbate psychiatric symptoms, understanding and addressing this issue is crucial.
“Increasing our understanding of this area could, with more research, lead to more effective treatments and ultimately improve people’s quality of life,” adds Malcangio.
George Sideris-Lampretsas, the study’s first author, echoes that sentiment, noting that the research is a key step in helping Alzheimer’s patients in their long-term care. “The results of this study have the potential to make a difference by identifying Galectin-3/TLR4 as a potential therapeutic target for chronic pain and, most importantly, by raising awareness about the underreported and untreated pain experienced by patients,” he says.
The study, published in the journal Nature Communications, was funded by the European Union’s Horizon 2020 Research and Innovation Programme.