Evaluation of analgesic effect synergistic between dopamine agonists and transcranial magnetic stimulation in fibromyalgia syndrome

Abstract

Fibromyalgia is a chronic painful syndrome defined as a diffuse pain in the whole body, associated with fatigue, non-restorative sleep and depression symptoms. In USA affects 2% of the population and in Brazil 2.5%. The Central Nervous System (CNS) probably mediates the majority of fibromyalgia symptoms. However, it is unknown if these central changes are primary or secondary in the pathophysiology of this disease. Several pharmacologic and non-pharmacologic treatments aiming CNS have been studied for this condition, showing low or medium efficacy in most part of the patients. Antidepressants that act on the serotonin and norepinephrine reuptake have showed partially efficacy in fibromyalgia pain. Similarly, anticonvulsant drugs such as pregabalin and gabapentin also had partial success in the treatment of fibromyalgia. However, many patients do not have a positive response to these therapies, besides the important side effects that these drugs can have. There are some clinical trials testing dopaminergic agonists to treat fibromyalgia, showing better results to these drugs when compared to pregabalin or gabapentin. Additionally, the use of repetitive transcranial magnetic stimulation (rTMS) has been studied at the last decade for the treatment of several diseases. Recently, a French research group showed beneficial effects of diary sessions of rTMS on the pain related to fibromyalgia, with pain relief of 30 to 40%. The mechanism of action of rTMS in pain is not fully understood. Recent studies have showed that rTMS probably act on the glutamartegic cortico-striatal pathways, and, in consequence, it would help on the release of dopamine. Recent studies have showed dopaminergic release after a TMS session. Besides the analgesic effect after a rTMS, almost 50% of the patients do not respond satisfactorily to the treatment.We hypothesis that a previous drug treatment with dopaminergic agonist might increase the analgesic effect of the rTMS, raising its efficacy and turning non-responder patients to responder ones. Thus, we design a study to evaluate the analgesic effect of the rTMS preceded or not by the use of a dopaminergic agonist, controlled by sham stimulation. Also, we measure the effect of a dopaminergic drug intake before the treatment through the cortical excitability, known as altered in fibromyalgia patients. (AU)