Investigation and Modulation of the Central Mu-Opioid Mechanism in Migraine (in vivo)
Although MRI-based techniques have provided insights into the function of brain regions involved in migraine, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding this process in vivo is crucial to determine the systems involved in the persistence and relief of migraine, especially the μ-opioidergic system, arguably one of the principal endogenous pain modulatory systems in the brain. Recent studies from our lab using positron emission tomography (PET) with a selective radiotracer for μ-opioid receptor (μOR), [11C]carfentanil, have demonstrated that there is a decrease in μOR availability (non-displaceable binding potential - μOR BPND) in the brain of migraine patients during the attacks. These results indicated activation of the endogenous opioid neurotransmission interacting with μOR due to the ongoing pain. Unfortunately, exogenous opioids are unable to selectively target those dysfunctional brain regions without inducing multiple adverse effects and functional impairments. In fact, prolonged opioid therapy has been associated with migraine endurance and worsening. Interestingly, our recent studies have also shown that modulation of such μ-opioid mechanisms can be accurately achieved using a noninvasive tool, namely transcranial direct current stimulation (tDCS), and that it can produce analgesic after-effects in chronic migraine, and other trigeminal pain disorders. Therefore, the main goals of our study are: First, to exploit the μ-opioidergic mechanisms in migraine patients and allodynia; Second, to determine whether 10 daily sessions of primary motor cortex (M1)-tDCS have a modulatory effect on acute and chronic pain measures in episodic migraine patients; and Third, to investigate whether repetitive active M1-tDCS induces/reverts μOR BPND changes in the descending inhibitory system, and whether those changes are correlated with migraine pain measures. The studies above represent a change in paradigm in migraine research, as we directly investigate and modulate in vivo one of the most important endogenous analgesic mechanisms in the brain.