This multicenter randomized controlled trial aims to evaluate the effectiveness of a multimodal intervention for the active management of persistent musculoskeletal pain in primary care. The intervention combines pain neuroscience education, therapeutic exercise, and the promotion of self-care and healthy lifestyle habits to improve health-related quality of life in adults with persistent nonspecific musculoskeletal pain lasting at least six months.

A total of 146 participants aged 18 to 70 years will be recruited from five primary care centers in the Comunitat Valenciana (Spain) and randomly assigned to either the experimental group or the control group. The primary outcome is health-related quality of life measured using the SF-36 Health Survey. Secondary outcomes include pain intensity, pain catastrophizing, kinesiophobia, central sensitization, emotional symptoms, perceived social support, medication use, and lifestyle-related variables. Assessments will be conducted at baseline, post-intervention, 6 months, and 12 months follow-up.

Persistent musculoskeletal pain represents a major public health problem and is one of the most frequent reasons for consultation in primary care. It is associated with reduced quality of life, functional limitations, emotional distress, increased healthcare utilization, and high socioeconomic costs. Contemporary pain science recognizes that persistent pain is a multidimensional experience involving biological, psychological, and social mechanisms, including central sensitization and maladaptive cognitive-emotional processes such as catastrophizing and fear-avoidance behaviors.

Current clinical practice guidelines recommend multimodal and non-pharmacological approaches as first-line management strategies. Pain neuroscience education (PNE) aims to reconceptualize pain by explaining the neurobiological and psychosocial mechanisms involved in persistent pain, thereby reducing perceived threat and maladaptive beliefs. Therapeutic exercise contributes to functional improvement, modulation of central pain mechanisms, and psychological well-being. Additionally, the promotion of self-care strategies and healthy lifestyle habits (including physical activity, sleep hygiene, stress management, and nutritional counseling) may enhance long-term outcomes and patient empowerment.

This study is a multicenter, parallel-group, single-blind randomized controlled trial conducted in five primary care centers in the Comunitat Valenciana (Spain). A total of 146 adults aged 18 to 70 years with nonspecific persistent musculoskeletal pain lasting at least six months will be recruited and randomly allocated to either an experimental group receiving the multimodal intervention or a control group receiving usual care.

The multimodal intervention integrates structured group-based pain neuroscience education sessions, supervised therapeutic exercise, and guidance on self-care and healthy lifestyle habits. The control group will continue to receive standard primary care management.

The primary outcome is health-related quality of life assessed using the SF-36 Health Survey. Secondary outcomes include pain intensity, number of painful areas, pain catastrophizing, kinesiophobia, central sensitization, emotional symptoms, perceived social support, medication consumption, and lifestyle-related variables. Data will be collected at baseline, immediately post-intervention, and at 6- and 12-month follow-ups using the REDCap electronic data capture system.

Statistical analyses will include descriptive statistics and inferential analyses to compare within- and between-group differences over time. The study aims to provide robust evidence regarding the effectiveness of a multimodal, biopsychosocial intervention delivered in primary care for the management of persistent musculoskeletal pain.

Inclusion Criteria:

• Adults aged between 18 and 70 years
• Diagnosis of nonspecific persistent musculoskeletal pain lasting at least 6 months
• Receiving care in participating primary care centers
• Ability to understand study procedures and provide written informed consent
• Ability to complete self-administered questionnaires

Exclusion Criteria:

• Specific musculoskeletal pathology requiring specialized treatment (e.g., fracture, inflammatory rheumatic disease, malignancy)
• Neurological disorders affecting movement or pain perception
• Severe psychiatric disorders that may interfere with participation
• Participation in another structured pain management program during the study period
• Cognitive impairment preventing questionnaire completion
• Pregnancy (if considered clinically relevant)

De-identified individual participant data (IPD) underlying the results reported in publications will be made available upon reasonable request. Data will be shared after publication of the primary results and will include variables necessary to reproduce the analyses. All shared data will be fully anonymized in accordance with applicable data protection regulations (including GDPR). Requests must include a methodologically sound research proposal and will require approval by the principal investigator and the corresponding ethics committee where applicable.

Outcome assessors responsible for statistical analysis will be blinded to group allocation. Due to the nature of the intervention, participants and care providers cannot be blinded.