The pathophysiology of migraine is complex and is still a focus of research. The main mechanisms of migraine are hypothalamic activation, alteration in thalamo-cortical circuits, altered brain connectivity, brainstem activation, cortical spreading depolarization, release of CGRP and PACAP .
A pool of analysis of the data from two programmes of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT 1 and 2)  with BoNT-A in chronic migraine demonstrated significant benefit of BoNT-A over placebo with regard to the numbers of headache days and migraine episodes. However, the effectiveness of botulinum therapy in the treatment of refractory migraine leaves much to be desired. Thus, the effectiveness of botulinum therapy in the treatment of refractory chronic migraine is about 37-50% [23-25]. With the exception of the reasons associated with the diagnosis, dose of the drug and the execution of the procedure, the main problem may be low individual susceptibility and neutralizing antibodies [26,27].
Cases of PRF GON have been described in two young women suffering from refractory migraine. They underwent botulinum therapy according to the PREEEMPT protocol at a dose of 155 units and at the same time a block of GON, then after a negative response, performed PRF GON with success in reducing pain intensity by twice for at least 3 months . Another case of a young 34-year-old woman who suffered from a complex headache of the type of chronic migraine, autonomic cephalgia, and occipital neuralgia. She was treated PRF DRG C2 with excellent effect throughout the year . Unfortunately, it is still unclear, whether she suffered mainly from migraines or whether the effectiveness of C2 RFA was associated with the successful treatment of occipital neuralgia.
An interesting question is whether it is possible to change PRF GON with a simpler and cheaper block of the GON, albeit performed repeatedly. There is evidence that a single injection of a local anesthetic can reduce the intensity of pain in chronic migraines, however, a low pain intensity in the study group should be noted - the decrease was from 3.93±1.8 to 1.55±1.42 mm VAS, also in this the study did not indicate whether the effect of a single block on the number of pain attacks or days with a headache . In a prospective multicenter study of 84 patients suffering from chronic migraine diagnosed according to the criteria of the IHS 2004 HCCC patients received 4 blocks of GON weekly. Researchers got a good effect in the form of reducing the number of days with a headache from 18 to 9 days a month, as well as reducing the intensity of pain during an attack. It is noteworthy that in the group of patients receiving placebo, there was also a decrease in the number of days with headache per month from 17 to 13, and a slight decrease in pain intensity. Nevertheless, it has been sufficiently convincingly proved that a series of GON blocks with bupivacaine effectively reduces the number of migraine attacks and the intensity of pain. As the study design was cross-sectional, and the treatment group patients received several more GON injections with bupivacaine, it is difficult to estimate how long-term this treatment is . Attempts have been described to treat chronic migraine with chronic neuromodulation of the GON. In a study of 66 patients whose CM was diagnosed using the second edition of the ICHD-II. After a positive response to the test block of GON, the best result was obtained in the group with adjustable neuromodulation, the decrease in the number of days with a headache was 27%. However, even such a good result, the best among the study groups still chronic migraine - the decrease was from 22.4±6.3 days to 15.7±10.0 days. The percentage of respondents - patients in whom the number of days with a headache decreased by 50% after stimulation in the best group by adaptive stimulation was 39% .
The main hypothesis of our study is that botulinum toxin reduces peripheral nociceptive afferentation and interrupts the release of inflammatory neuropeptides in the trigeminal complex with a further decrease in neurogenic inflammation of the vessels of the dura mater, which affects the trigeminovascular complex, and PRF affects the non-myelinated (C-fibers) and thinly myelinated (Aδ-fibers) axons, participating in the suppression of cortical depolarization through the system of trigeminocervical complex. Therefore, we associate the effectiveness of joint interventional treatment with the simultaneous impact on two main centers of regulation of mechanisms that ensure the emergence and maintenance of neurogenic inflammation and cortical depression - the trigeminovascular and trigeminocervical systems.
Limitations. The main limitation of this study is the small sample size of heterogeneous patients, short follow-up period and the absence of a comparison group. We should note that our patients were exposed to two invasive procedures therefore it might result in some placebo response distortion. Also we wish we had a larger sample size to strengthen our conclusions.