Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Neck Pain

Study Overview
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Brief Summary
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Structural brain alterations in pain-related areas have been demonstrated in patients with nonspecific 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 brain imaging biomarkers in patients with chronic nonspecific neck pain. The secondary objectives are to assess neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength.

Detailed Description
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This study is a single-blinded, randomized controlled trial. Forty-eight participants with chronic nonspecific 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 (2 visits per week). The control group will receive routine physical therapy. Primary outcomes are brain imaging biomarkers (cortical gray matter: volume, thickness and area, and white matter: fractional anisotropy and mean diffusivity) in pain-related areas. Secondary outcomes are neurochemical biomarkers (N-acetylaspartate, NAA; creatine, Cr; glutamic acid/glutamine, Glu/Gln; myoinositol, mI; and choline, cho), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength.

Official Title
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Effects of Manual Therapy Combined With Therapeutic Exercise on Brain Biomarkers in Patients With Chronic Nonspecific Neck Pain: Study Protocol for a Randomized Controlled Trial.

Conditions
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Neck Pain

Intervention / Treatment
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* Other: Manual therapy combinded with therapeutic exercise
* Other: Routine physical therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a history of nonspecific neck pain for ≥ 3 months an average pain intensity over the past week ≥ 35 mm. on a visual analogue scale (VAS) Exclusion Criteria: a history of head and neck injury or surgery known or suspected vestibular pathology or dizziness caused by underlying pathology in the ear, brain and sensory nerve pathways (e.g. benign paroxysmal positional vertigo) and/or vascular disorders any neurological or musculoskeletal condition that could affect the outcomes (e.g., scoliosis, torticollis, myofascial pain syndrome, fibromyalgia and rheumatoid arthritis) metabolic conditions (e.g., diabetes, obesity (BMI > 30 kg/m2) and hypertension) psychological symptoms (e.g., anxiety, depression and schizophrenia) contraindications to MRI (e.g., pregnancy/breastfeeding, claustrophobia and ferromagnetic implants) receiving physiotherapy treatment for their neck conditions in the past 12 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A single-blinded design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Manual therapy and therapeutic exercise | Other: Manual therapy combinded with therapeutic exercise<br>* The treatment includes cervical mobilization and specific therapeutic exercises: craniocervical and cervical flexors and extensors, axioscapular muscles, and postural correction (30-40 minutes). The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks).<br>|
| Experimental: Control group<br>Routine physical therapy | Other: Routine physical therapy<br>* The treatment includes routine physical therapy (e.g., modalities, range of motion and/or gentle stretching exercise) (30-40 minutes). The participants will attend 20 individual treatment sessions (2 visits per week for 10 weeks).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortical gray matter: volume and thickness | Cortical gray matter (volume and thickness) will be measured in pain-related areas (thalamus, prefrontal cortex (PFC), primary somatosensory cortex (S1), primary motor cortex (M1), insula, cingulate cortex, precuneus, temporal lobe and periaqueductal gray matter) using a Magnetic resonance imaging (MRI) machine | At baseline and post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurochemical biomarkers: N-acetylaspartate (NAA), creatine (Cr), glutamic acid/glutamine (Glu/Gln), myoinositol (mI), and choline (cho) | Neurochemistry biomarkers will be measured using single-voxel proton magnetic resonance spectroscopy (1H-MRS) in dorsolateral prefrontal cortex (DLPFC), primary somatosensory cortex (S1), anterior cingulate (ACC), insula and thalamus. | At baseline and post-intervention | 
| Neck pain intensity | The average intensity of neck pain will be assessed by using a 0-10 cm visual analogue scale (VAS), with 0 indicating no pain and 10 indicating worst imaginable pain. | At baseline and post-intervention | 
| Neck pain and disability | Neck Disability Index (NDI) will be used to assess how neck pain affects a patient's daily life and to assess the self-rated disability. A total score is 50, which a higher score indicates a higher disability. | At baseline and post-intervention | 
| Anxiety and depression | The symptoms of anxiety and depression will be assessed using Hospital Anxiety and Depression Scale (HADS). It includes two subscales: anxiety (HADS-A) and depression (HADS-D). A total score for each subscale ranges from 0 to 21, with higher scores indicating worse symptoms. | At baseline and post-intervention | 
| Cervical range of motion | Cervical range of motion (degrees) will be measured in flexion, extension, left-right lateral flexion and left-right rotation. | At baseline and post-intervention | 
| Cervical muscle strength | Cervical muscle strength will be measured in a craniocervical flexion action, using a handheld dynamometer (Newtons). | At baseline and post-intervention | 
| White matter integrity: fractional anisotropy (FA) and mean diffusivity (MD) | White matter in the brain will be quantified using diffusion tensor imaging (DTI) technique. | At baseline and post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neck pain, Manual therapy, Exercise, Magnetic resonance imaging, Magnetic resonance spectroscopy