“For most patients, pain control remains unsatisfactory,” explains Feng Pan, PhD, MMed, MBBS. “The few pharmacologic analgesic options available have limited efficacy and carry a substantial risk of adverse effects. Skeletal muscle—including its composition, quality, and function (strength)—has a role in knee osteoarthritis (OA) and pain pathophysiology. Exercises designed to improve muscle health are recommended by clinical guidelines for OA management, but the effect of exercise on pain reduction is modest. Previous studies, including those conducted by my colleagues and I, have demonstrated that populations with pain comprise homogeneous subgroups following distinct courses. These pain trajectories may reflect distinct patient subgroups who are clinically useful for the classification of patients with OA pain for tailored treatments.”

For a paper published in Pain, Dr. Pan and colleagues examined the association of lean mass and muscle strength and quality with a trajectory of approximately 10 years. A total of 947 participants from a population-based cohort study were analyzed. Dual-energy X-ray absorptiometry was used to assess lean and fat mass. Leg and knee extensor strength and lower-limb muscle quality were measured, calculated, or both. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire, and radiographic knee osteoarthritis (ROA) was assessed by X-ray.

Three Pain Trajectories Identified

The researchers identified three distinct trajectories: minimal pain (53%), mild pain (34%), and moderate pain (13%). They found that higher total and lower limb lean mass were associated with an increased risk for mild and moderate pain trajectories relative to the minimal pain trajectory, but these associations became non-significant after further adjustment for fat mass. “On the basis of the pain trajectories that we previously identified, we were able to observe what pain severity looks like at an individual level,” Dr. Pan says. “We then examined whether those muscle properties are associated with different pain courses.”

Total lean mass percentage was associated with a lower risk of mild pain (95% CI, 0.92-0.98) and moderate pain trajectory (95% CI, 0.87-0.96). Greater leg and knee extensor strength and muscle quality were associated with mild pain and moderate pain trajectories. Similar results were found in those with ROA. “Higher lower limb muscle strength and quality, and relative lean mass, were associated with a reduced risk of severe knee pain trajectories, suggesting that improving muscle function and composition may protect against persistent unfavorable knee pain courses,” Dr. Pan says.

The study team discovered that greater relative lean mass, muscle strength and quality, but not absolute lean mass, decreased the risk for worse pain courses. “Therefore, exercise interventions particularly designed to improve muscle composition, strength, and quality may shift pain trajectory from an unfavorable to a favorable course,” Dr. Pan notes. “In addition, we found a greater protective effect of higher lean mass percentage, muscle strength, and quality in those within the moderate pain trajectory compared with those in the mild pain trajectory. This suggests that current exercise therapy approaches need to be tailored to target a specific pain subpopulation.”

Targeting Risk Factors Early May Shift Pain Course

The level of pain within each trajectory does not markedly change over time, according to Dr. Pan. “This reflects that pain appears to be a non-progressive symptom and that pain levels at baseline are maintained over time,” he says. “Therefore, targeting important risk factors at baseline may shift pain courses (Table). Furthermore, we found that greater muscle strength and quality protect against worse pain courses and that these effects appear greater in more severe pain courses.”

Dr. Pan adds that the current study “highlights the importance of strengthening muscle in pain management and is crucially important for increasing the confidence to exercise in people with pain. In addition, exercise interventions for those with persistent moderate pain are more efficacious in improving pain course than interventions for those in the mild pain course. It would be worthwhile to examine whether exercise and/or diet interventions—particularly designed to improve muscle composition, strength, and quality—can shift pain trajectory from an unfavorable to a favorable course in further trials.”