Pain Phenotype in Knee Osteoarthritis: Implications for Mechanism-Based Therapy

Pain is the main symptom of knee osteoarthritis (KOA) and the main cause for patients to seek medical treatment. Despite the development of various therapies to address pain, its efficacy often remains uncertain. According to the new classification of the International Association for the Study of Pain, pain is classified as nociceptive pain, neuropathic pain and nociplastic pain. This review sought to outline potential mechanisms and clinical manifestations within this new classification framework and provided tailored treatment recommendations for each type of pain. Moreover, we further divided nociceptive pain into three subgroups including Inflammatory Pain, Mechanical Pain, and BMLs-related Pain. We suggest: (1) For inflammatory pain, the use of anti-inflammatory medications such as NSAIDs and corticosteroids is recommended. (2) For mechanical pain, weight loss, adjustments to mechanical alignment of the lower limb, and rehabilitation training may significantly alleviate symptoms. (3) For BMLs-related pain, patients might benefit from treatment, such as reducing weight-bearing and implementing antiosteoporosis drugs. (4) For neuropathic pain, management may involve tricyclic antidepressants or anticonvulsants. (5) For nociplastic pain, we give priority to nonpharmacological therapies, with an emphasis on the biopsychosocial model, and encourage patients to adopt positive lifestyle changes, including physical activity, weight management, sleep hygiene, and self-management, as well as involvement in psychotherapy and intervention. In clinical practice, it is essential to recognize that many patients may present with a combination of these pain types. Thus, it becomes imperative to identify the primary pain type and craft precise and individual treatment strategies tailored to their specific needs.