Mixed pain phenotypes in musculoskeletal disorders: mechanisms and management

Pain is categorized into three pain phenotypes: nociceptive, neuropathic and nociplastic, with overlapping pain referring to the coexistence of more than one pain phenotype. Overlapping pain occurs in more than one-third of individuals with musculoskeletal conditions, including inflammatory arthritis, osteoarthritis, spinal disorders and soft-tissue conditions. Whereas nociceptive pain is associated with identifiable tissue pathology and often responds to anatomically focused treatments, the presence of an additional pain phenotype, most commonly nociplastic pain, contributes to clinical complexity, poorer responses to conventional analgesics and procedures, and a greater burden of disease. Clinical identification of overlapping pain relies primarily on history-taking and physical examination, as no validated biomarker or widely accessible diagnostic test is currently available. Quantitative sensory testing and patient-reported questionnaires provide evidence of musculoskeletal overlapping pain but remain underutilized in routine practice. Once the underlying condition has been optimally managed, treatment should adopt a biopsychosocial approach that addresses comorbidities such as psychological distress, promotes self-efficacy and healthy lifestyle behaviours, and incorporates cautious use of pharmacological therapies. Effective clinical care requires recognition of overlapping pain as an important contributor to chronic musculoskeletal pain, with implications for treatment selection, including surgical and interventional decision-making, and for optimizing risk-benefit and cost-effectiveness outcomes.