Effects of manual therapy combined with therapeutic exercise versus routine physical therapy on brain biomarkers in patients with chronic non-specific neck pain in Thailand: a study protocol for a single-blinded randomised controlled trial

INTRODUCTION: Structural brain alterations in pain-related areas have been demonstrated in patients with non-specific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. The primary objective of this trial is to investigate the effects of manual therapy combined with therapeutic exercise on grey matter volume and thickness in patients with chronic non-specific neck pain. The secondary objectives are to assess changes in white matter integrity, neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength. METHODS AND ANALYSIS: This study is a single-blinded, randomised controlled trial. Fifty-two participants with chronic non-specific neck pain will be recruited into the study. Participants will be randomly allocated to either an intervention or control group (1:1 ratio). Participants in the intervention group will receive manual therapy combined with therapeutic exercise for 10 weeks (two visits per week). The control group will receive routine physical therapy. Primary outcomes are whole-brain and regional grey matter volume and thickness. Secondary outcomes are white matter integrity (fractional anisotropy and mean diffusivity), neurochemical biomarkers (N-acetylaspartate, creatine, glutamate/glutamine, myoinositol and choline), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength. All outcome measures will be taken at baseline and postintervention. ETHICS AND DISSEMINATION: Ethical approval of this study has been granted by Faculty of Associated Medical Science, Chiang Mai University. The results of this trial will be disseminated through a peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT05568394.