Specific Neck Rehabilitation for Unilateral Headache and Neck Pain, and Structural and Functional Changes in the Brain

In part 1 of the project clinical effect of specific neck rehabilitation for unilateral headache and neck pain (also termed cervicogenic headache) will be compared with standard primary health care. The researchers will further study whether fear avoidance beliefs and self-efficacy predict long term neck function and headache frequency superior to active range of neck movement. Part 2 will investigate whether patients with cervicogenic headache have structural changes in cerebral grey and white matter and in connectivity of the resting state state network, and whether these are reversed after effective neck rehabilitation and correlate to symptom severity and degree of disability.

The project includes two parts:

Part 1: With a longitudinal semicross-over, randomized control design the investigators will compare the clinical efficacy of a 6 month specific neck rehabilitation with standard primary health care on patients with unilateral headache and neck pain ( also termed cervicogenic headache) and study whether self-efficacy and fear avoidance beliefs predict 12 month self-reported neck function and headache frequency superior to the active range of neck movement The patients will either receive a specific neck rehabilitation program or 6 month standard primary health care before they cross over to neck rehabilitation. Sociodemographic and clinical characteristics will be collected before each treatment session and 6 and 12 months later.

Part 2: With a non-randomized comparative design including a subsample of the patients (n: 36) and healthy controls (n: 36) the investigators will explore whether there are structural changes in the cerebral grey and white matter, and whether cerebral connectivity within the default mode network (DMN and other major cerebral networks) are significantly different and whether the changes correlate to symptom severity and degree of disability.

Structural (cortical volume and thickness) changes will measured by volumetric magnetic resonance imaging (MRi) and diffusion tensor imaging (DTI), while cerebral connectivity by resting state fMRI (rs-fMRI). Whether the anticipated cerebral changes in volume, structure and connectivity are reversed after specific neck rehabilitation will be tested by repeated measurements. Analyses of MRI scans and clinical characteristics will be performed before each treatment session and 6 months later.

Statistics: Power calculations based on previous studies indicate that for the clinical part a number of 21 patients within each treatment group (a total of 42 patients) and for the MR analyses a subsample of 34 patients and 34 health controls will be sufficient to obtain a statistical power of 80% with a p-value of 5%. Due to a high drop out rate we have included a total of 57 patients. Changes between baseline and the 6 month follow up will be used for "between and within group" comparisons while 12 months data will be included for in "within-group" comparisons. Statistical predictor analyses will be performed by regression analyses. The statistician who are performing the primary end point analysis, are blinded to group assignment.

Eligibility Criteria:
Inclusion Criteria:

* Unilateral headache and neck pain for 2 years or more
* Minimum one headache attack pr week (numeric rating scale ≥4)
* Five or more of Antonaci's seven diagnostic criteria
* Neck Disability Index score ≥8 Points (≥16 percent points).

For healthy controls:

• Same age distribution

Exclusion Criteria:

* Progressive diseases (rheumatoid arthritis, cancer)
* Ongoing cervical infection
* Neurological disease (syringomyelia, radiculopathy, multiple sclerosis, Parkinson's disease, ischemic stroke )
* Other headache (\>1 tension type headache or migraine attack every month)
* Other pain conditions (including primary temporomandibular disorder and generalized pain (fibromyalgia with pain intensity \>6 to digital palpation)
* Previous or ongoing drug abuse
* Serious psychiatric disorder.
* Hopkins Symptom Checklist-25 score for depressive symptoms \> 2.2
* Ongoing litigation process
* Intolerance to MRI
* Pregnancy and lactation
* For the subsample undergoing MR analyses: Other systemic diseases (Hypertension, hyperlipidemia, diabetes mellitus, heart disease, cerebrovascular, epilepsy or other vascular diseases) and dysmenorrhea requiring analgesics

For healthy controls:

* Exclusion criteria as above
* Chronic pain
* Chronic dizziness
* Intolerance to MRI
* Pregnancy and lactation