Although MRI-based techniques have provided insights into the function of brain regions involved in migraine, there is little understanding of he 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 ?-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 ?-opioid receptor (?OR), [11C]carfentanil, have demonstrated that there is a decrease in ?OR availability (non-displaceable binding potential - ?OR BPND) in the thalamus, and other pain-related regions, in the brains of migraineurs during the headache (ictal) and non-headache (interictal) phases. The thalamus is the major relay structure in the forebrain for (non)-noxious inputs, which will be distributed subsequently to multiple cortical areas for discriminative, cognitive and affective processing. 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 ?-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. However, the electric fields generated by its most conventional analgesic montage are widely spread across the brain, lacking specificity on the pain-related structures directly targeted. Recently, a novel high-definition tDCS (HD- tDCS) montage (Villamar et al., 2013) created by our group based on epidural M1 stimulation principles reduced exclusively contralateral sensory-discriminative clinical pain measures (pain intensity/area) in chronic trigeminal pain patients. Therefore, the main goals of our study are: First, to exploit the ?-opioidergic dysfunction in vivo in migraine patients and allodynia compared to healthy controls; second, to determine whether 10 daily sessions of non-invasive and precise M1 HD-tDCS have a modulatory effect on clinical and experimental pain measures in episodic migraine patients; and third, to investigate whether repetitive active M1 HD-tDCS induces/reverts ?OR BPND changes in the thalamus and other pain-related regions, 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.

Public Health Relevance

In this study, our team of researchers will investigate the impact of migraine suffering on the endogenous - opioid system in vivo, arguably one of the principal endogenous pain modulatory systems in the brain, and its modulation by 10 daily sessions of primary motor cortex stimulation using high-definition transcranial direct current stimulation (HD-tDCS).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS094413-01
Application #
9008329
Study Section
Special Emphasis Panel (NOIT)
Program Officer
Oshinsky, Michael L
Project Start
2015-09-30
Project End
2020-08-31
Budget Start
2015-09-30
Budget End
2016-08-31
Support Year
1
Fiscal Year
2015
Total Cost
$373,367
Indirect Cost
$132,485
Name
University of Michigan Ann Arbor
Department
Biology
Type
Schools of Dentistry
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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DaSilva, Alexandre F; Nascimento, Thiago D; Jassar, Hassan et al. (2017) Dopamine D2/D3 imbalance during migraine attack and allodynia in vivo. Neurology 88:1634-1641
Cummiford, Chelsea M; Nascimento, Thiago D; Foerster, Bradley R et al. (2016) Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients. Arthritis Res Ther 18:40
DosSantos, Marcos F; Ferreira, Natália; Toback, Rebecca L et al. (2016) Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes. Front Neurosci 10:18
DaSilva, Alexandre F; Truong, Dennis Q; DosSantos, Marcos F et al. (2015) State-of-art neuroanatomical target analysis of high-definition and conventional tDCS montages used for migraine and pain control. Front Neuroanat 9:89