Mixed Pain: Toward a Consensus Definition and a Mechanism-Based Framework.

Knee osteoarthritis (OA) is a chronic pain condition affecting nearly 16% of the US adult population, with prevalence increasing with age. OA is characterized by degenerative processes within the joint, yet research has shown that pain and functional disability relate weakly to joint pathology., , Pain varies widely in knee OA due to changes in the peripheral and central nervous system,, , leading to pain sensitization as evidenced by allodynia, hyperalgesia, and inefficient pain inhibition., Altered pain sensitivity has been reported in numerous cohort studies, and associates with greater clinical pain reporting and poor health outcomes., , , However, the factors underlying pain sensitization in knee OA are only partially understood, and new evidence suggests that changes within periarticular tissues, such as fibrosis and intramuscular fat infiltration, may contribute nociceptive input via inflammatory pathways leading to pain sensitization., Nociceptors are widely dispersed within the periarticular tissues (eg, muscle and connective tissues) and can be activated by inflammatory mediators (eg, bradykinin, interleukin‐6 [IL‐6], IL‐8, IL‐15, and tumor necrosis factor α) present in knee OA, as well as by adipokines secreted from adipose tissues within the joint (eg, fat pad), and local muscle tissues., , , Recent studies have reported greater intramuscular adipose tissue within the quadriceps is positively associated with knee joint pain and degeneration., , Also, changes in thigh muscle activation and recruitment (eg, loss of motor control and muscle fatigability), can inhibit synergistic motor functions necessary for knee joint stability and control, which may result in a temporary lessening of pain, but ultimately result in greater inflammation, joint compressive forces, and subsequent pain. Applying the pain adaptation theory to knee OA, knee pain will cause underutilization of the agonist muscle (eg, quadriceps) and overutilization of the antagonist muscle (eg, hamstrings). Recent findings show this pattern of muscle co‐contraction between the quadriceps and hamstrings in patients with knee OA is associated with greater pain sensitization linking aberrant motor control with pain sensitivity via shared central mechanisms. Knee OA is associated with functional decline characterized by reduced lower limb strength, impaired gait, and compromised knee stability. The quadriceps and hamstring muscle groups play complementary roles in dynamic knee support and joint stabilization. Examining periarticular tissue structures (ie, quadriceps and hamstrings) were selected as representative anterior and posterior thigh muscles due to their biarticular function and documented involvement in functional outcomes in knee OA. Previous studies have reported increased biceps femoris activation during specific phases of gait in individuals with knee OA, which was interpreted as a compensatory strategy to enhance joint stability in the presence of quadriceps weakness. Strengthening interventions targeting both quadriceps and hamstrings have been shown to improve pain and functional outcomes in knee OA, underscoring the importance of these muscle groups in disease pathology,, and pain in knee OA. Myotonometry (MyotonPro) is a noninvasive and clinically accessible measure of biomechanical and viscoelastic soft tissue properties. It uses the mechanical dynamic response method in which a brief mechanical impulse is applied to the skin to quantify different oscillation parameters based on tissue responses, including (1) the natural frequence of the acceleration signal (tone); (2) the tissue's resistance to the external force of the probe, calculated using the damped natural oscillation response by a built‐in accelerometer (stiffness); (3) tissue elasticity (inversely proportional to decrement), determined by sequential oscillations when the tissue restores its shape following deformation from the repeated probe tapping; (4) relaxation time, the time it takes for a muscle to recover its shape following a voluntary contraction or after an external force is removed; and (5) creep, the gradual elongation of tissue over time when placed under constant tensile stress. There is typically an inverse relationship between tone and stiffness with relaxation time and creep. Tone and stiffness are often highly correlated with each other, as are relaxation time and creep. Together, these measures provide insight into the structural properties and function of both the superficial muscle and overlying soft tissues, including adipose tissue and fascia. To date, two studies have used myotonometry to assess quadriceps tone and stiffness in persons with knee OA. Results indicated increased muscle stiffness in persons with knee OA compared to healthy controls, which was associated with greater symptom burden based on a clinical measure of pain and function (ie, Western Ontario and McMaster Universities Arthritis Index [WOMAC] total score)., Howe