Sex Differences in Estradiol Secretion by Trigeminal Brainstem Neurons

Estrogen status is a significant risk factor in the development of temporomandibular joint disorders (TMD). Classically, estrogen status is thought to derive mainly from ovarian sources; however, it is well known that estradiol (E2) also is synthesized by neurons in the brain. This study tested the hypothesis that E2 is produced by neurons in trigeminal subnucleus caudalis (Vc), the principal site of termination for sensory afferents that supply the temporomandibular joint (TMJ), to modify evoked responses in a model of TMJ nociception in male and female rats. Intra-TMJ injection of the small fiber excitant, allyl isothiocyanate (AIC), increased the levels of E2 collected from microdialysis probes sites at Vc of ovariectomized (OvX) female rats, ipsilateral to the stimulus, whereas males displayed no change. Dialysate levels of E2 collected from probe sites in the contralateral Vc or cerebellum in OvX rats were not affected by TMJ stimulation. Reverse dialysis of anastrozole, an aromatase (ARO) inhibitor, via the probe reduced perfusate levels of E2 in Vc. Systemic administration of letrozole, a non-steroid ARO inhibitor, for 4 days prevented TMJ-evoked increases in masseter muscle electromyography (MMemg) activity. ARO-positive neurons were distributed mainly in superficial laminae (I-III) at Vc and cell counts revealed no significant difference between OvX and male rats. Intra-TMJ injection of AIC revealed similar numbers of ARO/Fos dual-labeled neurons in OvX and male rats. By contrast, the percentage of ARO neurons co-labeled for glutamic acid decarboxylase (GAD), the biosynthetic enzyme for GABA, was greater in OvX (35%) than male rats (14%). Few ARO-positive neurons were co-labeled for estrogen receptor alpha. These data indicate that E2 is secreted continuously by Vc neurons and that acute stimulation of TMJ nociceptors evokes further secretion in a sex-dependent manner. Reduced TMJ-evoked MMemg activity after ARO inhibition suggests that locally produced E2 by Vc neurons acts via paracrine mechanisms to modify TMJ nociception in female rats

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

Reconhecimento antecipado de problemas ortográficos em escreventes novatos: quando e como acontecem

A aprendizagem da ortográfica constitui um processo complexo, envolvendo questões lexicais e gramaticais. Muitos estudos sobre essa aprendizagem tratam os problemas ortográficos de modo independente e separado da produção textual. Neste estudo defendemos a importância de se analisar a aprendizagem da ortografia a partir da perspectiva proposta pela Genética Textual, colocando em destaque a gênese do processo de escritura e criação textual. Apresentamos o Sistema Ramos, metodologia de investigação que registra o processo de escritura em tempo e espaço real da sala de aula. Esse Sistema oferece informações multimodais (fala, escrita, gestualidade) sobre o que alunos, em duplas, reconhecem como problemas ortográficos (PO) e os comentários espontâneos feitos quando estão escrevendo o texto. Este estudo analisa justamente o momento em que aconteceram esses reconhecimentos e os comentários de duas alunas no 2º ano de escolaridade, durante a produção de seis histórias inventadas. Mais do que uma análise quantitativa dos tipos de PO identificados no produto, apresentamos uma análise enunciativa e microgenética de reconhecimentos de PO e seus comentários, particularmente aqueles PO antecipados pelas escreventes. Os resultados indicam: i. Reconhecimentos ensejam comentários nem sempre relacionados ao PO identificado; ii. Reconhecimentos e comentários estão relacionados aos conteúdos ortográficos ensinados em sala de aula; iii. Alguns PO reconhecidos envolvem a articulação de diferentes níveis linguísticos. Esses aspectos podem contribuir para a compreensão da aprendizagem da ortografia em situações didáticas propiciadas pela escrita colaborativa a dois.The acquisition of spelling competence is a complex process, involving lexical and grammatical questions. Research, however, almost always places the spelling from an autonomous point of view and disconnected from the other components of writing. In this text, we present the relevance of the Ramos System that captures students in an ecological situation of text production in pairs, allowing access to the processes for solving orthographic problems. Collaborative writing also grants access to comments made by students during the process of textual linearization. Our study focuses on the recognition of spelling problems (SP) and the comments made regarding such problems by two 2nd grade students during the production of six invented stories. More than a quantitative analysis of the types of SP identified in the product, we were interested in making a qualitative and fine analysis of oral recognitions of SP, particularly those SP anticipated by the writers. Our results indicate that: i. Recognition motivates comments that are not always related to the identified SP; ii. Recognition and comments are related to the orthographic contents taught in the classroom; iii. Some of the recognized SP involve the articulation between different linguistic levels. These aspects can contribute for the comprehension of orthographic learning in didactic situations provided by collaborative writing.publishe

PRZEDRUK POLSKIEGO TŁUMACZENIA ARTYKUŁU ZA ZGODĄ INTERNATIONAL ASSOCIATION FOR THE STUDY OF PAIN (IASP) - PAIN 154 (2013) 1057-1064 Status względem estrogenu oraz stres psychofizyczny modyfikują informację płynącą ze stawu skroniowo-żuchwowego do neuronów rogów tylnych rdzenia kręgowego w sposób swoisty dla blaszki u samic szczurów

Estrogen status and psychological stress contribute to the expression of several chronic pain conditions including temporomandibular muscle and joint disorders (TMJD). Sensory neurons that supply the temporomandibular joint (TMJ) region terminate in laminae I and V of the spinal trigeminal nucleus (Vc/C1-2 region); however, little is known about lamina-specificity and environmental influences on the encoding properties of TMJ brainstem neurons. To test the hypothesis that Vc/C1-2 neurons integrate both interoceptive and exteroceptive signals relevant for TMJ nociception, we recorded TMJ-evoked activity in superficial and deep laminae of ovariectomized rats under high and low estradiol (E2) and stress conditions. Rats received daily injections of low (LE) or high (HE) dose E2 and were subjected to forced swim (FS) or sham swim conditioning for 3 days. The results revealed marked lamina-specificity in that HE rats displayed enhanced TMJ-evoked activity in superficial, but not deep, laminae independent of stress conditioning. By contrast, FS conditioned rats displayed increased background firing and TMJ-evoked activity of neurons in deep, but not superficial, laminae independent of E2 status. FS also enhanced TMJ-evoked masseter muscle activity and suggested the importance of deep dorsal horn neurons in mediating evoked jaw muscle activity. In conclusion, E2 status and psychophysical stress play a significant role in modifying the encoding properties of TMJ-responsive medullary dorsal horn neurons with a marked laminaspecificity.Status względem estrogenu oraz stres psychologiczny wpływają na ekspresję kilku schorzeń przebiegających z bólem przewlekłym, w tym schorzeń mięśni i stawów skroniowo-żuchwowych. Neurony czuciowe, które zaopatrują okolicę stawu skroniowo-żuchwowego (temporomandibular joint, TMJ ) kończą Wykorzystasię w blaszkach I i V jądra rdzeniowego nerwu trójdzielnego (obszar Vc/C1-2); niewiele jednak wiadomo na temat swoistości tych blaszek lub oddziaływań środowiskowych na własności kodowania neuronów pnia mózgu związanych z TMJ. W celu sprawdzenia hipotezy, zgodnie z którą neurony Vc/C1-2 integrują zarówno interoceptywne jak i eksteroceptywne sygnały istotne dla nocycepcji z TMJ, rejestrowaliśmy aktywność neuronów w blaszkach powierzchownych i głębokich wywołaną przez drażnienie TMJ u szczurów po owariektomii, w warunkach dużego i małego stężenia estradiolu (E2) i podczas stresu. Szczurom wstrzykiwano codziennie małe (LE) lub duże (HE) dawki E2 i przez 3 dni poddawano warunkowaniu w postaci wymuszonego pływania (forced swimming, FS ) lub pływania pozorowanego. Wyniki wykazały znaczącą swoistość blaszek w tym znaczeniu, że szczury otrzymujące HE wykazywały zwiększoną, wywołaną drażnieniem TMJ aktywność w blaszkach powierzchownych (ale nie głębokich) niezależnie od warunkowania stresem. W przeciwieństwie do tego szczury warunkowane FS wykazywały zwiększone wyładowania wyjściowo i zwiększoną, wywołaną drażnieniem TMJ aktywność neuronów w blaszkach głębokich (ale nie powierzchownych) w sposób niezależny od statusu względem E2. Wymuszone pływanie zwiększało również wywołaną drażnieniem TMJ aktywność mięśnia żwacza, co wskazuje na znaczenie neuronów blaszek głębokich rogów tylnych w pośredniczeniu w wywołanej aktywności mięśni związanych z żuciem. Wyciągamy stąd wniosek, że status względem E2 oraz stres psychofizyczny odgrywają istotną rolę w modyfikowaniu własności kodowania w neuronach rogów tylnych rdzenia kręgowego reagujących na drażnienie TMJ ze znaczącą swoistością blaszek