Brain Micro- and Macro-Structural Characteristics Investigation in Fibromyalgia Using Multi-Modal Magnetic Resonance Imaging

Fibromyalgia (FM) is a chronic widespread pain condition that deeply impacts the lives of patients. Multiple symptoms such as fatigue, impaired cognition, and sleep disturbances among others are commonly described. Despite intensive research effort, no disease-specific mechanism uniquely explains the clinical presentation of FM. Nonetheless, current evidence points to a major role of the central nervous system for the main feature of this condition: pain and sensory augmentation. Neuroimaging techniques provide a window into the brain mechanisms that may play a role in FM. Several studies using functional magnetic resonance imaging (MRI) show abnormalities in pain processing in the brain of FM patients. Likewise, structural abnormalities are found using anatomical MRI however the findings are less consistent. The main goal of this dissertation was to comprehensively assess brain structural features of FM patients and matched controls at both micro- (cellular-level structures such as membranes, myelin as well as axonal density) and macro-structural (gross anatomical) levels as measured by diffusion-weighted and high-resolution anatomical MRI respectively. The results from diffusion MRI show evidence of widespread micro-structural white matter (WM) abnormalities in the brains of FM patients compared to controls, and also within relevant pain-related brain regions. These findings give support to the view that alterations in the brain of patients potentially contribute to the symptoms experienced by them. Conversely, macro-structural brain features showed little difference between patients and controls regarding gray matter (GM) characteristics. Between-group differences were only found for increased volume in the amygdalae and WM adjacent to the anterior cingulate cortex and left insula for FM patients relative to controls. Taken together these findings may indicate that structural abnormalities in the brain of FM patients are more widespread in the micro-structural level, while regional differences limited to subcortical structures and WM adjacent to pain-related cortical areas are more typical at the macro-structural level with no measurable impact to GM morphological characteristics.Doctor of Philosoph

Evaluation of a magnetic resonance-compatible dentoalveolar tactile stimulus device

<p>Abstract</p> <p>Background</p> <p>Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature.</p> <p>Results</p> <p>A novel device capable of delivering valid and reliable dentoalveolar somatosensory stimulation was developed (ICC = 0.89, 0.78-1 [95% CI]). Psychophysical data analysis showed high discriminant ability in differentiating painfree controls from cases with chronic dentoalveolar pain related to deafferenting dental procedures (sensitivity = 100%, specificity = 86.7%, area under ROC curve = 0.99). FMRI results of dentoalveolar dynamic pressure pain in painfree subjects revealed activation of brain areas typically associated with acute pain processing including thalamus, primary/secondary somatosensory, insular and prefrontal cortex.</p> <p>Conclusions</p> <p>A novel psychophysical method to deliver dynamic dentoalveolar pressure stimulation was developed and validated, allowing non-invasive MRI-based exploration of central nervous system function in response to intraoral somatosensation.</p> <p>Background</p> <p>The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood <abbrgrp><abbr bid="B3">3</abbr><abbr bid="B4">4</abbr><abbr bid="B5">5</abbr></abbrgrp>. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) <abbrgrp><abbr bid="B6">6</abbr><abbr bid="B7">7</abbr></abbrgrp>, is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology <abbrgrp><abbr bid="B8">8</abbr><abbr bid="B9">9</abbr><abbr bid="B10">10</abbr></abbrgrp>, but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" <abbrgrp><abbr bid="B7">7</abbr></abbrgrp>.</p> <p>Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain <abbrgrp><abbr bid="B11">11</abbr></abbrgrp>. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long-term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain.</p> <p>In the past few years several studies used fMRI to investigate the human trigeminal system <abbrgrp><abbr bid="B12">12</abbr><abbr bid="B13">13</abbr></abbrgrp>, with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation <abbrgrp><abbr bid="B14">14</abbr></abbrgrp> or only teeth <abbrgrp><abbr bid="B15">15</abbr><abbr bid="B16">16</abbr><abbr bid="B17">17</abbr></abbrgrp>. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner <abbrgrp><abbr bid="B17">17</abbr><abbr bid="B18">18</abbr></abbrgrp>: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli <abbrgrp><abbr bid="B19">19</abbr></abbrgrp>, as reliability/reproducibility is a necessary feature of sensory testing <abbrgrp><abbr bid="B20">20</abbr></abbrgrp>.</p> <p>Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI.</p

Frequency of Nonodontogenic Pain after Endodontic Therapy: A Systematic Review and Meta-Analysis

Little is known about ill-defined pain that persists following endodontic procedures, including an estimate of the problem’s magnitude. We conducted a systematic review of prospective studies that reported the frequency of non-odontogenic pain in patients who had undergone endodontic procedures

Frequency of Persistent Tooth Pain after Root Canal Therapy: A Systematic Review and Meta-Analysis

Little is known about the frequency of persistent pain after endodontic procedures, even though pain is a core patient-oriented outcome. We estimated the frequency of persistent pain, regardless of etiology, following endondontic treatment

Frequency of Persistent Tooth Pain after Root Canal Therapy: A Systematic Review and Meta-Analysis

Little is known about the frequency of persistent pain after endodontic procedures, even though pain is a core patient-oriented outcome. We estimated the frequency of persistent pain, regardless of etiology, following endondontic treatment

Perceptual and Neural Response to Affective Tactile Texture Stimulation in Adults with Autism Spectrum Disorders

Autism spectrum disorders (ASD) are associated with differences in sensory sensitivity and affective response to sensory stimuli, the neural basis of which is still largely unknown. We used psychophysics and functional magnetic resonance imaging (fMRI) to investigate responses to somatosensory stimulation with three textured surfaces that spanned a range of roughness and pleasantness in a sample of adults with ASD and a control group. While psychophysical ratings of roughness and pleasantness were largely similar across the two groups, the ASD group gave pleasant and unpleasant textures more extreme average ratings than did controls. In addition, their ratings for a neutral texture were more variable than controls, indicating they are less consistent in evaluating a stimulus that is affectively ambiguous. Changes in brain blood oxygenation level-dependent (BOLD) signal in response to stimulation with these textures differed substantially between the groups, with the ASD group exhibiting diminished responses compared to the control group, particularly for pleasant and neutral textures. For the most unpleasant texture, the ASD group exhibited greater BOLD response than controls in affective somatosensory processing areas such as the posterior cingulate cortex and the insula. The amplitude of response in the insula in response to the unpleasant texture was positively correlated with social impairment as measured by the Autism Diagnostic Interview-Revised (ADI-R). These results suggest that people with ASD tend to show diminished response to pleasant and neutral stimuli, and exaggerated limbic responses to unpleasant stimuli, which may contribute to diminished social reward associated with touch, perpetuating social withdrawal, and aberrant social development

Pain inhibition is not affected by exercise-induced pain

Introduction: Offset analgesia (OA) and conditioned pain modulation (CPM) are frequently used paradigms to assess the descending pain modulation system. Recently, it was shown that both paradigms are reduced in chronic pain, but the influence of acute pain has not yet been adequately examined. Objectives: The aim of this study is to investigate OA and CPM after exercise-induced pain to evaluate whether these tests can be influenced by delayed-onset muscle soreness (DOMS) at a local or remote body site. Methods: Forty-two healthy adults were invited to 3 separate examination days: a baseline appointment, the consecutive day, and 7 days later. Participants were randomly divided into a rest (n 5 21) and an exercise group (n 5 21). The latter performed a single intensive exercise for the lower back. Before, immediately after, and on the following examination days, OA and CPM were measured at the forearm and the lower back by blinded assessor. Results: The exercise provoked a moderate pain perception and a mild delayed-onset muscle soreness on the following day. Repeatedmeasurements analysis of variance showed no statistically significantmaineffect for eitherOAorCPMat the forearmor lower back (P.0.05). Conclusion: Delayed-onset muscle soreness was shown to have no effect on the inhibitory pain modulation system neither locally (at the painful body part), nor remotely. Thus, OA and CPM are robust test paradigms that probably require more intense, different, or prolonged pain to be modulated

AUT696043_Supplementary_Material – Supplemental material for Initially intact neural responses to pain in autism are diminished during sustained pain

<p> Supplemental material, AUT696043_Supplementary_Material for Initially intact neural responses to pain in autism are diminished during sustained pain by Michelle D Failla, Estephan J Moana-Filho, Greg K Essick, Grace T Baranek, Baxter P Rogers and Carissa J Cascio in Autism </p