Chronic migraine (CM) is a very disabling disorder with grave socioeconomic consequences. Pharmacological approaches can affect mechanisms of pain production, while rehabilitation such as Transcutaneous Electrical Nerve Stimulation and Manual Therapy may reduce the neuromuscular contributing factors. The main aim of the study is to evaluate the effects of cervical and thoracic manipulative techniques combined with OnabotulinumtoxinA prophylaxis on headache frequency in patients with Chronic Migraine (CM). The second aim is to evaluate the training effects on the intensity of headache attacks, analgesic consumption, cervical range of motion, TrPs sensitivity and disability. The hypothesis is that the manipulative treatment would alleviate CM symptoms and, in turn, decrease the analgesic consumption.

The present study is a single-blind randomized controlled trial conducted according to the Declaration of Helsinki, the guidelines for Good Clinical Practice, and the Consolidated Standards of reporting Trials (CONSORT) Statement guidelines. The examiner will be blinded to group assignment. If eligible, patients will be allocated to the experimental group (EG) or the control group (CG) using an automated randomization system (Allocation ratio 1:1). The group allocation will be kept concealed by means of sealed numbered envelopes. The randomization list was locked in a desk drawer accessible only to the main investigator. All the treatments and assessment will be performed in the Neurorehabilitation Unit of Azienda Ospedaliera Universitaria Integrata of Verona (Italy).

Patients will be asked to complete a daily headache diary, which is routinely administered to all patients with CM admitted at our Unit for OnabotulinumtoxinA prophylaxis. In the context of this study, daily headache diaries during 1 month pre-treatment (T0), during the treatment (treatment phase) and 1 month post-treatment (T1) will be considered.

Moreover, at T0 a questionnaire concerning clinical and demographic data as well as some habits like consumption of coffee and alcohol, and smoking will be administered. According to the nature of the study feasibility and efficacy outcomes will be defined. Feasibility outcomes were the patients' compliance during treatments, any adverse events (i.e. pain, discomfort) occurred during the treatment, and the number of training session performed. Primary and secondary outcome measures will be categorized as efficacy outcomes.

Inclusion criteria will be:

• age between 18 and 65 years;
• diagnosis of CM according to fhe International Classification of Headache Criteria-III;
• ineffective assumption of at least 3 different drug classes recommended by the international guidelines of migraine treatment;
• intolerance to/inefficacy of primary prophylaxis therapy;
• prophylactic treatment with OnabotulinumtoxinA according to the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol;
• at least two consecutive OnabotulinumtoxinA injections.

Exclusion criteria will be:

• contraindications to onaBoNTA injection;
• presence of other neurologic disorders that can cause/sustain migraine;
• onaBoNTA treatment for purposes other than those of this study;
• other non-pharmacological treatments for migraine (e.g. massage, acupuncture);
• severe and unstable cardiovascular and cerebrovascular disease;
• presence of infections, psychiatric diseases or functional disorders in any head structure;
• severe osteoporosis;
• vertebral or arm fractures; alcohol/drug abuse;
• relevant medical therapy changes during the trial;
• incomplete headache diaries with missing information.