Pain in Spinal Muscular Atrophy: A systematic review

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular disorder caused primarily by homozygous deletions or mutations in the SMN1 gene, leading to survival motor neuron protein deficiency and progressive degeneration of anterior horn alpha motor neurons. This neurodegenerative process results in muscle weakness, atrophy, and varying degrees of respiratory and orthopedic complications.Historically, SMA has not been considered a pain-predominant condition; however, emerging evidence from observational studies, patient registries, and clinical trials indicates that pain is a significant yet underrecognized comorbidity in individuals with SMA. With the advent of disease-modifying therapies, including antisense oligonucleotides, gene replacement therapy, and small-molecule splicing modifiers, patients are experiencing extended survival and improved motor function, consequently altering the natural history of the disease and its pain manifestations.This systematic review aims to synthesize current evidence on the prevalence, characteristics, underlying mechanisms, and clinical impact of pain in SMA across all age groups and phenotypes. We systematically searched major biomedical databases for studies reporting pain outcomes, assessment tools, and management strategies in SMA (PROSPERO registration: CRD420251118178).Findings reveal that pain affects 40-80% of patients, predominantly manifesting as musculoskeletal discomfort associated with scoliosis, joint contractures, and prolonged wheelchair use, as well as neuropathic and iatrogenic pain components. Despite its high prevalence, pain in SMA remains inadequately assessed and undertreated, lacking standardized evaluation protocols or evidence-based management guidelines. This review underscores the need for multidisciplinary approaches integrating pharmacological, rehabilitative, orthopedic, and psychological interventions, and highlights future research directions aimed at developing SMA-specific pain assessment instruments and personalized therapeutic strategies to improve quality of life.