1. 2017;20;139-154Does Conservative Treatment Change the Brain in Patients with Chronic Musculoskeletal Pain? A Systematic Review
   Systematic Review
   Mira Meeus, PhD, Barbara Cagnie, PhD, Robby DePauw, PT, MSc, Anneleen Malfliet, PT, MSc, Jo Nijs, PhD, Lieven Danneels, PhD, MSc, Iris Coppieters, PT, MSc, and Jeroen Kregel, MSc.

BACKGROUND: Chronic musculoskeletal pain is characterized by maladaptive central neuroplastic changes. Many observational studies have demonstrated that chronic pain states are associated with brain alterations regarding structure and/or function. Rehabilitation of patients with chronic musculoskeletal pain may include cognitive, exercise, or multimodal therapies.

OBJECTIVE: The current review aims to provide a constructive overview of the existing literature reporting neural correlates, based on brain magnetic resonance imaging (MRI) techniques, following conservative treatment in chronic musculoskeletal pain patients.

STUDY DESIGN: Systematic review of the literature.

METHODS: The current review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Literature was searched from 3 databases and screened for eligibility. Methodological quality across studies was assessed with Cochrane Collaboration’s tool for assessing risk of bias and quality of evidence was determined applying the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

RESULTS: A total of 9 eligible studies were identified with a predominant high risk of bias. Cognitive behavioral therapy induced several structural and functional changes predominantly in prefrontal cortical regions and a shift from affective to sensory-discriminative brain activity after behavioral extinction training. Multidisciplinary treatment in pediatric complex regional pain syndrome facilitated normalization of functional connectivity of resting-state networks and the amygdala, and increased gray matter in prefrontal and specific subcortical areas. Exercise therapy led to specific for resting-state functional connectivity and a trend towards pressure-induced brain activity changes.

LIMITATIONS: A very small number of studies was available, which furthermore exhibited small study samples. Moreover, only 2 of the included studies were randomized controlled trials.

CONCLUSIONS: It is likely that conservative treatments may induce mainly functional and structural brain changes in prefrontal regions in patients with chronic musculoskeletal pain. Due to the relatively high risk of bias across the included studies, future studies with randomized designs are needed to confirm the current findings. In addition, more research evaluating the treatment-induced effects on white matter and whole-brain network dynamics are warranted.

Key words: Chronic pain, musculoskeletal pain, MRI, functional MRI, therapy, rehabilitation, cognitive behavioral therapy, exercise therapy