3D-Neuronavigation <em>In Vivo</em> Through a Patient's Brain During a Spontaneous Migraine Headache

Abstract

A growing body of research, generated primarily from MRI-based studies, shows that migraine appears to occur, and possibly endure, due to the alteration of specific neural processes in the central nervous system. However, information is lacking on the molecular impact of these changes, especially on the endogenous opioid system during migraine headaches, and neuronavigation through these changes has never been done. This study aimed to investigate, using a novel 3D immersive and interactive neuronavigation (3D-IIN) approach, the endogenous µ-opioid transmission in the brain during a migraine headache attack in vivo. This is arguably one of the most central neuromechanisms associated with pain regulation, affecting multiple elements of the pain experience and analgesia. A 36 year-old female, who has been suffering with migraine for 10 years, was scanned in the typical headache (ictal) and nonheadache (interictal) migraine phases using Positron Emission Tomography (PET) with the selective radiotracer [ 11 C]carfentanil, which allowed us to measure µ-opioid receptor availability in the brain (non-displaceable binding potential -µOR BP ND ). The short-life radiotracer was produced by a cyclotron and chemical synthesis apparatus on campus located in close proximity to the imaging facility. Both PET scans, interictal and ictal, were scheduled during separate mid-late follicular phases of the patient's menstrual cycle. During the ictal PET session her spontaneous headache attack reached severe intensity levels; progressing to nausea and vomiting at the end of the scan session. There were reductions in µOR BP ND in the pain-modulatory regions of the endogenous µ-opioid system during the ictal phase, including the cingulate cortex, nucleus accumbens (NAcc), thalamus (Thal), and periaqueductal gray matter (PAG); indicating that µORs were already occupied by endogenous opioids released in response to the ongoing pain. To our knowledge, this is the first time that changes in µOR BP ND during a migraine headache attack have been neuronavigated using a novel 3D approach. This method allows for interactive research and educational exploration of a migraine attack in an actual patient's neuroimaging dataset.

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

“…In humans, similar changes in FC where found in high frequent episodic migraineurs between PAG and PFC (Solstrand and Dahlberg et al, 2018). We previously demonstrated an increase in μ-opioid receptor-mediated neurotransmission in PAG and mPFC during a spontaneous EM attacks and allodynia (DaSilva et al, 2014a, DaSilva et al, 2014b), when compared to the interictal phase. Herein, when ictal CM attacks where compared with HCs during thermal challenge, we noticed that μ-opioid system activity was also increased in the thalamus and caudate, confirming that important brain regions generally involved in sensory processing and modulation of pain are also affected at the circuit level, facilitating ascending cephalic pain inputs with inefficient inhibitory pain modulatory responses to external stimuli (Jia and Yu., 2017; Wunderlich et al, 2011).…”

“…So far, the only direct investigation of endogenous μ-opioid activation in vivo was done with positron emission tomography (PET) in EM patients with allodynia. This study showed a decrease in μOR non-displaceable binding potential (BP ND ) with [ 11 C]carfentanil (DaSilva et al, 2014a). μOR BP ND is a selective measurement of μOR availability in vivo , and its immediate decrease during EM headache attack (ictal phase) and allodynia mostly suggested the existence of a transitory increase in ictal activation of endogenous μ-opioid neurotransmission in the periaqueductal gray matter (PAG) and medial prefrontal cortex (mPFC), rather than a sharp change in the number of μOR (DaSilva et al, 2014b; Nascimento et al, 2014).…”

Functional imaging and migraine

“…56–58 Indicating that there is endogenous opioid release during a migraine attack, these studies have shown reduced mu-opioid non-displaceable binding potential in the cingulate cortex, nucleus accumbens, thalamus, periaqueductal gray, and medial prefrontal cortex. 56, 57 …”

The Forefront of Dentistry—Promising Tech-Innovations and New Treatments

“…However, step by step, they are contributing to dental education, research, and treatment. For example, data from brain imaging of patients during pain can be visualized by students in virtual reality to have a more immersive educational experience (DaSilva et al 2014). The same applies with orthognathic surgical simulation methods when combined with traditional records, showing positive attitudes from the students toward higher-fidelity tools concerning visualization, manipulation, and enjoyment of the task (Sytek et al 2021).…”