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July/August 2024
July/August 2024 Issue Orthopedics: Understanding Osteoarthritic Pain and Cognitive Impairment Researchers work to see whether there’s a link between osteoarthritic pain and cognitive ability. Chronic pain affects millions of individuals worldwide each year. In 2021 in the United States alone, more than 50 million adults experienced chronic pain, which is pain lasting more than three months. Of those individuals, the CDC found that 17.1 million had pain so severe it restricted their activities of daily living. One of the most common causes of pain and disability is osteoarthritis. According to the World Health Organization, “Osteoarthritis is a degenerative joint condition. It causes pain, swelling and stiffness, affecting a person’s ability to move freely. Osteoarthritis affects the entire joint, including the tissues around it. It’s most common in the knees, hips, spine, and hands,”1 The World Health Organization also notes that in 2019, 528 million people worldwide had osteoarthritis, a more than 100% increase from 1990. Rates of osteoarthritis are expected to continue climbing as the population continues to age—the majority of individuals with osteoarthritis are older than the age of 55—and as other risk factors, such as obesity, increase, as well. Thus, researchers are often looking to better understand osteoarthritis, its risk factors, symptoms, and common comorbidities. Recently, researchers at the University of Nottingham in the United Kingdom looked at the relationship between osteoarthritis pain and cognitive functioning, with the goal of finding out whether the former led to the latter. Cognitive Functioning While a natural decline in some areas of cognitive functioning is expected, a more severe cognitive impairment is typically the result of something besides the aging process. A cognitive impairment is characterized by an individual’s struggle with cognitive functioning, often in terms of memory loss and ability to focus. The condition most commonly linked, and in fact defined, by cognitive impairment is Alzheimer’s disease. However, cognitive impairment is not solely a symptom of Alzheimer’s and other forms of dementia. There are many other reasons for an individual to see a decline in cognitive functioning. The link between cognitive impairment and chronic pain is well documented. “Numerous cross-sectional studies have reported poorer overall performance in cognition in people with chronic pain. Compared with the general elderly population, people with chronic pain often have memory deficits, reduced attention, disorientation, executive dysfunction, and impaired emotional decision making,”2 according to an evidence review published in the National Library of Medicine in 2023. Tobias Bast, PhD, faculty of science at the University of Nottingham, agrees, citing the connection as motivation for the study on osteoarthritic pain and cognitive impairment. “There has been a long [list of] literature on cognitive impairment in many conditions that are characterized by pain, and if you ask people who have pain, including patients who are a part of the PPI (Patient and Public Involvement) group at our pain center, they say ‘Yeah, cognitive impairment is a problem for me.’ But there was not actually any specific evidence that osteoarthritic pain, pain you get from knee arthritis, specifically, causes cognitive impairment,” he says. The University of Nottingham’s Pain Centre Versus Arthritis opened in 2010 and specifically investigates what leads to chronic pain. For the study, “We started out with the hypothesis that knee pain by itself would also cause cognitive impairment—the idea that pain does impair cognition,” Bast explains. Research Methods and Outcome Bast refers to a study also from the University of Nottingham that followed nearly 1,000 patients newly diagnosed with osteoarthritis over seven years. The results indicated that social deprivation, which can be a byproduct of chronic pain, and limited educational attainment are associated with cognitive impairment and difficulty with activities of daily living. The experimental method used in this study relied on Lister hooded rats rather than humans. By using rats, the researchers were able to focus exclusively on knee pain and cognitive function without other factors, such as age, social deprivation, and more blurring the potential connection between the two. The rats, which were all male, were separated into two cohorts. This allowed the researchers to assess different cognitive functions. The study, which was published in The Journal of Pain in August 2023, states that “Study 1 used the watermaze delayed-matching-to-place (DMP) task of rapid place learning, which is highly sensitive to hippocampal dysfunction, and study 2 used the NOR [novel object recognition] memory test, which depends on medial temporal lobe structures, including the hippocampus and perirhinal cortex, and an operant task of behavioral flexibility, which depends on PFC [prefrontal cortex] function. Cognitive testing was complemented by measurements of pain behavior (weight-bearing asymmetry and vonFrey test of paw-withdrawal threshold [PWT]) and of sensorimotor processes.”3 The rats received an injection in their left knees to mimic the pain that might be felt by a patient with osteoarthritis. The rats were tested for cognitive functioning on day zero and multiple times over the course of the next several weeks. The specific timeline for retesting varied depending on the cohort the rats were in. Based on the data gathered, the researchers concluded that their hypothesis that osteoarthritic knee pain alone would cause cognitive impairment was incorrect. Implications and Further Research However, individuals with osteoarthritis are experiencing a decline in cognitive functioning. “We need to ask ourselves why do these patients show cognitive impairment,” he says. “Our hypothesis is there is an interaction of pain and age. As I mentioned, in our human samples, participants were on average 63 or 64 and osteoarthritis is of course mostly affecting older people. One possibility is that for the pain really then to cause cognitive impairment, your system, your brain, already need to be primed by age—a little bit preimpaired. And if this comes together, then this results in cognitive impairment,” Bast explains. “Or there could be other factors, such as medication. People will have a history of pain medication. That could induce changes in the nervous system that then makes participants more susceptible to the cognitive impairment caused by pain,” he continues. The key to determining what is causing the cognitive functioning to decline is additional research, both with humans and in control groups with animals. Bast sees the potential for answers in the animal model. “These factors you can partly tease apart in an animal model. For example, we could now study our animal model of knee pain in aged rats and see if we take a group of aged rats with knee pain, are they impaired compared to a group of aged rats without that knee pain. We could also see if these animals have had a pretreatment, say with opioid pain killers. Does that make them more susceptible to the knee pain causing cognitive impairment?” he says. As more research is completed, the results, whether they indicate a causal connection or not, will help inform the medical profession’s understanding of osteoarthritis, cognitive functioning and the symptoms, comorbidities, and risk factors that accompany both. — Sue Coyle, MSW, is a freelance writer in the Philadelphia suburbs.
References 2. Chen J. Wang X, Xu Z. The relationship between chronic pain and cognitive impairment in the elderly: a review of current evidence. J Pain Res. 2023;16:2309-2319. 3. Goncalves S. Hathway GJ, Woodhams SG, Chapman V, Bast T. No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain. J Pain. 2023;24(8):1478-1492. |
