Dr. Alex DaSilva has received his Doctor in Medical Science degree in Oral Biology with clinical training in Trigeminal Pain at Harvard University, which was followed by a post-doctoral on Migraine Neuroimaging at the Martinos Center for Biomedical Imaging, Massachusetts General Hospital. He currently has a background in magnetic resonance imaging (MRI) methods (e.g. fMRI, DTI), and their application in pain research. The main goal of this K23 project is to provide Dr. DaSilva advanced mentoring and training on molecular neuroimaging, technology only available in selected institutions, to establish a solid independent scientific and academic career. In this project, we will integrate anatomical MRI techniques with positron emission tomography (PET) for the study of structural and molecular cortical neuroplasticity in migraine, as well as the allodynic mechanisms associated with it. The fact that many therapeutic modalities do not provide relief for these treatment-resistant patients raises the possibility that the cause for the chronicity of these debilitating disorders may lie in the brain itself, and possibly in the dysfunction of specific cortical and subcortical areas (e.g. SI, periaqueductal gray matter) and modulatory mechanisms (e.g. opioidergic mechanisms). Recent studies with PET using a selective mu-opioid receptor (MOR) radiotracer, have shown varied pattern of reduced MOR binding potential (BP) depending on the disorders investigated (e.g. fibromyalgia). These findings represent either higher occupation of MOR by endogenous ligands or loss of opioid receptors. Interestingly, our last results suggest that such molecular changes in refractory pain parallel cortical thickness and diffusional changes in areas related to pain perception and modulation in episodic migraine patients. Therefore, we will test the hypothesis that migraine is sustained by mal-adaptive changes at multiple levels of the cortex by pursuing the following Aims: 1) To investigate MOR-BP changes in chronic trigeminal pain patients compared to healthy controls;2) To demonstrate that frequency of the headache attacks and severity of cutaneous allodynia levels in migraineurs are correlated with MORBP.3) To investigate whether MORBP levels in the PAG of migraineurs are associated with changes in the gray matter thickness changes in cortical areas associated with pain perception and modulation.

Public Health Relevance

As a career goal, this multidisciplinary training project will help to establish my research as an independent scientist applying PET and MRI-based neuroimaging in the study of cellular and molecular neuroplastic- ssocited mechanisms in migraine, as well as cutaneous allodynia. This project is expected to expand our knowlegde on cortical migraine pathophysiology, and possibly novel therapeutic targets in the brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23NS062946-04
Application #
8332305
Study Section
NST-2 Subcommittee (NST)
Program Officer
Porter, Linda L
Project Start
2009-08-15
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$160,790
Indirect Cost
$11,910
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
Nascimento, Thiago D; DosSantos, Marcos F; Danciu, Theodora et al. (2014) Real-time sharing and expression of migraine headache suffering on Twitter: a cross-sectional infodemiology study. J Med Internet Res 16:e96
Nascimento, Thiago D; DosSantos, Marcos F; Lucas, Sarah et al. (2014) ?-Opioid activation in the midbrain during migraine allodynia - brief report II. Ann Clin Transl Neurol 1:445-50
DaSilva, Alexandre F; Nascimento, Thiago D; DosSantos, Marcos F et al. (2014) Migraine and the Mu-opioidergic system-Can we directly modulate it? Evidence from neuroimaging studies. Curr Pain Headache Rep 18:429
DaSilva, Alexandre F; Nascimento, Thiago D; Love, Tiffany et al. (2014) 3D-neuronavigation in vivo through a patient's brain during a spontaneous migraine headache. J Vis Exp :
DaSilva, Alexandre F; Nascimento, Thiago D; DosSantos, Marcos F et al. (2014) Association of ?-Opioid Activation in the Prefrontal Cortex with Spontaneous Migraine Attacks - Brief Report I. Ann Clin Transl Neurol 1:439-444
Dasilva, Alexandre F; Mendonca, Mariana E; Zaghi, Soroush et al. (2012) tDCS-induced analgesia and electrical fields in pain-related neural networks in chronic migraine. Headache 52:1283-95
DaSilva, A F; DosSantos, M F (2012) The role of sensory fiber demography in trigeminal and postherpetic neuralgias. J Dent Res 91:17-24