BACKGROUND AND AIMS: Globally, chronic low back pain (CLBP) affects 70-80% of adults at some point in their lives and current treatments are widely unsuccessful in relieving pain. Understanding the underlying neurophysiological (e.g., descending pain inhibition) and biobehavioral (e.g., stress) processes contributing to chronic pain in patients with CLBP is needed for the development of novel treatments. Previous studies have shown that acute stress can impact pain sensitivity and that childhood trauma may predispose a person to CLBP, but the mechanisms underlying this impact are unknown. Conditioned Pain Modulation (CPM) is a psychophysical paradigm used in research to assess descending pain modulatory pathways, which are thought to be impaired in patients with CLBP as well as in those with childhood trauma. The overlap of conditions has not been explored. The current study explored the impact of childhood trauma on the CPM response within a sample of patients with CLBP being treated at a tertiary pain clinic. CLBP patients exposed to an acute stress paradigm were expected to shower higher pain sensitivity, with acute stress significantly interacting with a history of childhood trauma as a factor leading to the higher pain sensitivity. METHODS: 46 Participants with CLBP (n=46, mean age=49 years, 55.3% female) recruited from a pain treatment service completed a Quantitative Sensory Testing (QST) and CPM before and after an acute psychological stressor. Participants were randomized to a control (n=25) or an acute-stress (n=21) condition. The acute-stress condition included the Stroop Color Word Task (SCWT) and a mental arithmetic task prior to completing the QST protocol a second time. The control participants did not undergo any additional stressors and completed the QST protocol a second time after a 20-minute break. Participants’ CPM response was measured by the average change in pressure pain threshold (PPT) from baseline to the conditioning stimulus (non-dominant hand in ice-water bath). A “Good CPM response” was defined as a CPM effect above 100, indicating that the pain threshold increased when exposed to the conditioning stimulus. To examine the impact of childhood trauma on pain sensitivity, participants completed a Childhood Traumatic Events Scale (CTES) to assess the presence and severity of six types of trauma (death, parental upheaval, sexual, violence, illness or injury, other upheaval) during childhood. The CTES was scored as a continuous variable by calculating the sum the trauma severity for all six trauma types. RESULTS: A large majority of the sample (94% of participants) showed an increase in pain threshold during hand immersion in ice water, which was contrary to our hypothesis based on prior research done on other chronic pain conditions and CLBP. Participants exposed to an acute stressor had an impaired CPM effect compared to those that were not exposed to an acute stressor, however there was no difference between groups (p=0.277). A history of childhood traumatic events did not correlate significantly with an impaired baseline CPM or a change in CPM effect when exposed to an acute stressor. CONCLUSION: The current study used novel QST modalities, including CPM, to analyze the interaction between acute and chronic stress on pain sensitivity. Ultimately, this study found that exposure to an acute stressor had a negative effect on CPM, indicating that when under experimental stress participants were more sensitive to pain compared to when they were not under stress, although the findings were not statistically significant. These findings should be further investigated to expand the understanding of the neurophysiological mechanisms underlying CLBP and to potentially provide novel treatment modalities for patients with CLBP.

No description available.

L'objectif de notre travail était dans un premier temps d'étudier les liens entre l'altération des fibres nerveuses de petit diamètre et la présence de douleurs chez des patients ayant une neuropathie périphérique. Notre deuxième objectif était d'évaluer la pertinence de certaines techniques neurophysiologiques pour mettre en évidence l'atteinte de ces petites fibres nerveuses. Notre première étude réalisée sur une large cohorte de patients présentant divers types de neuropathie a montré, grâce à une étude quantifiée de la sensibilité, qu'il n'y avait pas de corrélation entre la perte ou perte de fonction des fibres nerveuses de petit diamètre et la présence de douleurs. Ceci a été confirmé par notre deuxième étude portant sur une population plus homogène de patients ayant une neuropathie amyloïde familiale et étudiés avec une batterie neurophysiologique plus large. Ainsi, les douleurs neuropathiques des patients présentant une neuropathie périphérique sont probablement dues à la combinaison de facteurs d'hyperexcitabilité périphérique et de sensibilisation centrale et non directement liée à la perte en petites fibres. Il reste cependant pertinent de développer des techniques objectives d'exploration de ces petites fibres notamment dans un but de diagnostic clinique. Notre troisième étude a montré que certaines méthodes neurophysiologiques étaient particulièrement sensibles dans ce cadre en prenant pour exemple la détection d'anomalies précoces d'atteinte des petites fibres au cours de la neuropathie amyloïde familiale. Une batterie de tests comprenant l'enregistrement des potentiels évoqués laser, la mesure du seuil de détection du chaud et de la conductance cutanée, s'est avérée être la combinaison la plus pertinente, comme l'a montré notre quatrième étude sur une grande cohorte de patients susceptibles de présenter une neuropathie des petites fibres. / The aim of our work was initially to study the relationship between alterations in small diameter nerve fibers and the presence of pain in patients with peripheral neuropathy. Our second objective was to assess the relevance of some neurophysiological tests to characterize these alterations in small nerve fibers. Our first study of a large cohort of patients with various types of neuropathy showed, using quantitative sensory testing, that there was no correlation between the loss or loss of function of small nerve fibers and the presence of pain. This was confirmed by our second study focused on a more homogeneous population of patients with familial amyloid neuropathy and studied with a larger neurophysiological battery. Thus, neuropathic pain in patients with peripheral neuropathy is probably due to a combination of factors of peripheral hyperexcitability and central sensitization and not directly related to the loss of small nerve fibers. However, it remains relevant to develop techniques of objective investigation of these small nerve fibers for a purpose of clinical diagnosis. Our third study showed that some neurophysiological methods were particularly sensitive in this context, taking the example of the detection of early alteration of small nerve fibers in familial amyloid neuropathy. A battery of tests, including laser evoked potential recording, warm detection threshold and electrochemical skin conductance measurement, proved to be the most appropriate combination for this diagnostic purpose, as shown by our fourth study on a large cohort of patients likely to have a small fiber neuropathy.

<p>In a prospective randomised double-blind study eighty patients with MRI verified lumbar disc herniation and corresponding clinical findings underwent microscopic disc removal. The patients were peroperatively given systemic and local corticosteroids or placebo, and followed for 2 years. The hospital stay and time to return to full-time work was significantly shorter in the treatment group. Pain measured as worst pain during the last week was also lower in the corticosteroid group. The results indicate that peroperative treatment with corticosteroids reduces pain and improves the functional outcome in patients operated for lumbar disc herniations.</p><p>To evaluate whether thermal quantitative sensory testing (QST) is applicable in the study of sensory dysfunction in lumbar disc herniations 66 patients with disc herniations underwent thermal QST. We found that thermal QST reflects sensory dysfunction in patients with lumbar disc herniations. However, thermal QST seems to have a poor predictive value for identifying the anatomic location of a herniated lumbar disc.</p><p>Quantitative sensory testing (QST) was used to detect damage to the myelinated A-delta fibres (cold sense) and the unmyelinated C-fibres (warmth sense). Corticosteroids combined with surgery in lumbar disc surgery improved the normalisation for the warmth disturbance compared to the control group. </p><p>A prospective analysis was performed on the predictive value of preoperatively determined lumbar lordosis and flexion for pain and disability in patients treated by microscopic lumbar disc surgery. Preoperative hyperlordosis correlated to more pain postoperatively (p=0.004). In patients with hypoflexion there was an association between hyperlordosis and moderate or severe pain postoperatively (p<0.001). The same outcomes were found for DRI. The stiff and straight back indicates a good outcome of lumbar disc surgery concerning pain and disability. </p>

In a prospective randomised double-blind study eighty patients with MRI verified lumbar disc herniation and corresponding clinical findings underwent microscopic disc removal. The patients were peroperatively given systemic and local corticosteroids or placebo, and followed for 2 years. The hospital stay and time to return to full-time work was significantly shorter in the treatment group. Pain measured as worst pain during the last week was also lower in the corticosteroid group. The results indicate that peroperative treatment with corticosteroids reduces pain and improves the functional outcome in patients operated for lumbar disc herniations. To evaluate whether thermal quantitative sensory testing (QST) is applicable in the study of sensory dysfunction in lumbar disc herniations 66 patients with disc herniations underwent thermal QST. We found that thermal QST reflects sensory dysfunction in patients with lumbar disc herniations. However, thermal QST seems to have a poor predictive value for identifying the anatomic location of a herniated lumbar disc. Quantitative sensory testing (QST) was used to detect damage to the myelinated A-delta fibres (cold sense) and the unmyelinated C-fibres (warmth sense). Corticosteroids combined with surgery in lumbar disc surgery improved the normalisation for the warmth disturbance compared to the control group. A prospective analysis was performed on the predictive value of preoperatively determined lumbar lordosis and flexion for pain and disability in patients treated by microscopic lumbar disc surgery. Preoperative hyperlordosis correlated to more pain postoperatively (p=0.004). In patients with hypoflexion there was an association between hyperlordosis and moderate or severe pain postoperatively (p&lt;0.001). The same outcomes were found for DRI. The stiff and straight back indicates a good outcome of lumbar disc surgery concerning pain and disability.

No description available.

Thesis (MNutr (Human Nutrition))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: Background Patients with chronic renal failure must deal not only with the disease itself, but also have to follow a strict dietary regimen. In South Africa there is currently a great demand for new and updated recipes based on the South African Renal Exchange Lists. The focus of this research was the development and testing of recipes commonly used by renal patients following a westernised diet. Objectives The main objectives of the study were to develop and test recipes that meet the nutritional requirements of patients with chronic renal failure. The secondary objectives were to determine the gender and racial differences in participants’ responses during consumer sensory testing. Methodology The study population consisted of patients with chronic renal failure on hemodialysis and continuous ambulatory peritoneal dialysis from Tygerberg Academic Hospital (TAH). Data was collected in three phases, using census sampling: Phase 1 included the development and adaptation of recipes to suit the renal diet. Phase 2 included the consumer sensory testing of the recipes by the dialysis patients, using the 9-point hedonic scale. Phase 3 included the rating of the recipes, the final nutritional analysis and allocation of renal exchanges to one portion of each recipe, as well as the final formatting of the recipe to make it more user-friendly for the renal patient. Results In total, 45 patients took part in the sensory evaluation of 30 recipes. Eighty percent of the subjects were coloured, 4% were white while 16% were black. Fifty-one percent (n=23) were female and 49% (n=22) were male. Of the 30 recipes that were evaluated for overall acceptance, appearance, smell, texture and taste, only 7 were deemed unacceptable. Recipes were unacceptable when less than 80% of the study participants gave a mean overall score of more than 6. Significant differences in the overall acceptability scores were found between the male and female subgroups for the Fish and Vegetable Pie (p=0.031), Chicken Pilaf (p=0.008) and Date Fingers (p=0.002). The females showed a greater preference for these two main meals while the males showed a greater preference for the Date Fingers. Significant differences were found between the black and westernised subgroups for the Rice Salad (p=0.006), Wheat and Mushroom Casserole (p=0.022), Curried Wheat Salad (p=0.043) and the Coconut Ice (p=0.005), with the westernised subgroup showing a greater preference for the dishes than the black subgroup. Conclusion The 23 recipes that were acceptable to the study participants are recommended for inclusion in the RenalSmart Software programme. These recipes are suitable for patients following a westernised diet. It is proposed that recipes suitable for the black and Indian population must be developed in future research. / AFRIKAANSE OPSOMMING: Agtergrond Pasiënte met chroniese nierversaking moet nie net slegs die siektetoestand hanteer nie, maar moet ook ‘n streng dieet regime volg. Daar is huidiglik in Suid-Afrika ‘n groot behoefte vir nuwe en opgedateerde resepte gebasseer op die Suid-Afrikaanse Nier Ruillyste. Die fokus van hierdie navorsing was om resepte te ontwikkel en te toets wat algemeen ingeneem word deur nierversaking pasiënte wat ‘n westerse dieet volg. Doelwitte Die hoof doelwitte van die studie was om resepte te identifiseer en te toets wat voldoen aan die nutrisionele behoeftes van nierpasiënte met kroniese nierversaking. Die sekondêre doelwitte was om geslag en ras verskille in die deelnemers se reaksies tydens verbruiker sensoriese evaluering te bepaal. Metodologie Die studie populasie het bestaan uit pasiënte met chroniese nierversaking op hemodialise en aaneenlopende ambulatoriese peritoneale dialise van Tygerberg Akademiese Hospitaal (TAH). Data was versamel in drie fases deur gebruik te maak van sensus steekproeftrekking: Fase 1 het die ontwikkeling en aanpassings van die resepte, om dit toepaslik te maak vir die nier dieet, ingesluit. Fase 2 het die verbruiker sensoriese evaluering van die resepte deur die dialise pasiënte, met behulp van die 9-punt hedoniese skaal, ingesluit. Fase 3 het die klassifisering van die resepte, die finale nutrisionele analise en die toekenning van nier ruile per porsie van elke resep, sowel as die finale formatering om die resep meer gebruikersvriendelik te maak vir die nierpasiënt, ingesluit. Resultate In totaal het 45 pasiënte aan die sensoriese evaluering van die 30 resepte deelgeneem. Tagtig persent van die deelnemers was kleurling, 4% was wit en 16% was swart. Een en vyftig persent (n=23) was vroulik en 49% (n=22) was manlik. Van die 30 resepte wat geevalueer is vir algehele aanvaarding, voorkoms, reuk, tekstuur en smaak, was slegs 7 onaanvaarbaar gevind. Resepte is as onaanvaarbaar beskou indien minder as 80% van die deelnemers ‘n gemiddelde algehele telling van meer as 6 gegee het. Beduidende verskille in die algehele aanvaarbaarheid tellings is gevind tussen die mans en vroue vir die Vis en Groente Pastei (p=0.031), Hoender Pilaf (p=0.008) en Dadelvingers (p=0.002). Die vrouens het ‘n groter voorkeur vir die twee hoofgeregte getoon terwyl die mans ‘n groter voorkeur vir die Dadelvingers getoon het. Beduidende verskille is gevind tussen die swart en westerse sub-groepe vir die Rysslaai (p=0.006), Koring en Sampioen Kasserol (o=0.022), Kerrie Koringslaai (p=0.043) en die Klapperys (p=0.005), met die westerse sub-groep wat ‘n groter voorkeur vir dié geregte toon as die swartes. Gevolgtrekking Die 23 resepte wat aanvaarbaar gevind is sal voorgestel word om ingesluit te word in die RenalSmart Sagteware program. Die resepte is toepaslik vir pasiënte wat ‘n westerse dieet volg. Daar word voorgestel dat resepte toepaslik vir die swart en Indiër populasie ontwikkel word in toekomstige navorsing.

Introdução: Embora a completa fisiopatologia da SDM permaneça desconhecida, evidências sugerem que na dor crônica os sistemas inibitórios são deficitários, como demonstrado pelo enfraquecimento da inibição intracortical do córtex motor. No entanto, a desinibição intracortical pode ser parcialmente revertida pelo tratamento com técnicas de estimulação cerebral não invasiva, tais como a estimulação magnética transcraniana repetitiva (EMTr). Embora estudos com EMTr tenham mostrado resultados promissores, poucos têm avaliado simultaneamente seus efeitos em medidas comportamentais, bioquímicas e neurofisiológicas. Assim, neste estudo avaliamos o efeito da EMTr na dor e, considerando a sua ação na função dos sistemas inibitórios corticais e intra-corticais, também investigamos parâmetros de excitabilidade cortical e níveis do mediador de neuroplasticidade BDNF, após tratamento com EMTr ou intervenção sham, em indivíduos com SDM crônica. Objetivos: Comparar o efeito de 10 sessões de EMTr ao da intervenção sham na função das vias nociceptivas cortical e subcortical (limiares de excitabilidade cortical e limiares termoalgésicos periféricos), na capacidade funcional, na qualidade do sono, nos níveis de dor, no sistema modulatório descendente de dor e nos níveis séricos de BDNF, em indivíduos com dor crônica miofascial do complexo craniocervicomaxilar. Assim, a hipótese deste estudo é que 10 sessões de EMTr, quando comparada com intervenção sham está associada com melhora nos níveis de dor, em indivíduos com dor crônica miofascial do complexo craniocervicomaxilar. Métodos: Vinte e quatro participantes do sexo feminino, com idades entre 19-65 anos, diagnosticadas com SDM do complexo craniocervicomaxilar por pelo menos 3 meses anteriores ao recrutamento e que evidenciaram componente neuropático (escore igual ou maior a quarto no DN4 – questionário para diagnóstico de dor neuropática), foram randomizadas para receber dez sessões de estimulação magnética transcraniana repetitiva (EMTr) (n = 12) de 10 Hz ou intervenção sham (n = 12). O estudo avaliou se a dor [limiares termoalgésicos (QST)], o sistema inibitório descendente [modulação condicionada da dor (QST + CPM)], a excitabilidade cortical (parâmetros da EMT) e o BDNF foram alterados após a intervenção. Resultados: Houve interação significativa (tempo versus grupo) em relação aos escores de dor, evidenciados pela escala análoga visual analógica de dor (EVA) (análise de variância, P<0,01). Análise post hoc mostrou que, em comparação com intervenção sham, o tratamento com EMTr reduziu em 30,21% os escores diários de dor (95% intervalo de confiança [IC] de -39,23 - -21,20) e em 44,56% o uso de analgésicos (-57,46 - -31,67). Comparado com o sham, o grupo que recebeu EMTr ativa aprimorou o sistema corticoespinal inibitório (redução de 41,74% no QST+CPM, P<0,05), reduziu em 23,94% a facilitação intracortical (P=0,03), aumentou em 52,02% o potencial evocado motor (P=0,02) e apresentou aumento de 12,38 ng/ml no nível sérico de BDNF (IC 95%=2,32-22,38). O grupo que recebeu EMTr demonstrou aumento na média dos escores B-PCP:S (P<0.03), redução de 45% no número de doses analgésicas diárias (P<0.003) e melhora na qualidade do sono (P<0.01). Nenhum efeito adverso foi observado. Conclusões: O tratamento com 10 sessões de EMTr de alta frequência (10 Hz) foi associado com significativa melhora na SDM crônica. EMTr reduziu os escores de dor, diminuiu o uso de analgésicos e melhorou a qualidade do sono. Os resultados do estudo também sugerem que os efeitos analgésicos da EMTr na SDM crônica foram mediados por mecanismos top-down regulation, que aumentaram a atividade do sistema corticoespinal inibitório, bem como a secreção de BDNF. / Introduction: Although the complete pathophysiology of MPS remains unknown, cumulative evidences suggest that in chronic pain the inhibitory systems are defective, as indexed by the weakening motor cortex intracortical disinhibition. The intracortical disinhibition can be partially reverted by treatment with noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS). Although rTMS studies have shown promising results, few ones have assessed simultaneously its effect on behavioral, biochemical and neurophysiological measures. Thus, this study assessed the effect of rTMS on pain and, considering its action on the function of the inhibitory cortical and intracortical systems, this trial also evaluated cortical excitability parameters and levels of a neuroplasticity mediator BDNF, after rTMS treatment or a sham intervention in patients with chronic MPS. Objectives: To compare the effect of 10 sessions of rTMS with sham intervention effects in the cortical and subcortical nociceptive pathways (cortical excitability parameters and peripheral thermoalgesic thresholds), in the functional capacity, quality of sleep, pain levels, descending pain modulatory system and in BDNF serum levels in patients with chronic myofascial pain of jaw-cranial-cervical complex. Thus, the hypothesis of this study is that 10 sessions of rTMS, when compared with sham intervention result in improvement in pain levels in subjects with chronic myofascial pain of jaw-cranial-cervical complex. Methods: Twenty-four female aged 19-65 diagnosed with MPS of jaw-cranial-cervical complex for at least three months prior to recruitment and with neuropathic pain component (score equal or higher than four in the DN4 - neuropathic pain diagnostic questionnaire) were randomized to receive ten sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). The study tested if pain [quantitative sensory testing (QST)], the descending inhibitory systems [conditioned pain modulation (QST+CPM)], the cortical excitability (TMS parameters) and the brain-derived neurotrophic factor (BDNF) have changed after intervention. Results: There was a significant interaction (time vs. group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on pain (analysis of variance, P<0.01). Post hoc analysis showed that compared with sham intervention, the treatment decreased daily pain scores by 30.21% (95% confidence interval [CI] -39.23 - -21.20) and analgesic use by 44.56 (-57.46 - -31.67). Compared to sham intervention group, the rTMS group enhanced the corticospinal inhibitory system (41.74% reduction in QST+CPM, P<0.05), decreased by 23.94% the intracortical facilitation (P=0.03), and showed an increase of 52.02% the motor evoked potential (P=0.02) and presented 12.38 ng/mL higher serum BDNF (95%CI=2.32 - 22.38). rTMS group showed an increase in mean scores B-PCP: S (P <0.03), 45% reduction in the number of daily analgesic doses (P <0.003) and significantly better sleep quality (P <0.01). No adverse event was observed. Conclusions: The treatment with 10 sessions of high-frequency rTMS (10 Hz) was associated with significant improvement in chronic MPS. rTMS reduced pain scores, lowered analgesic use and improved sleep quality. The results also suggested that the rTMS analgesic effects in chronic MPS were mediated by top-down regulation mechanisms enhancing the activity of the corticospinal inhibitory system and that this effect involved an increase in BDNF secretion.

Introdução: Embora a completa fisiopatologia da SDM permaneça desconhecida, evidências sugerem que na dor crônica os sistemas inibitórios são deficitários, como demonstrado pelo enfraquecimento da inibição intracortical do córtex motor. No entanto, a desinibição intracortical pode ser parcialmente revertida pelo tratamento com técnicas de estimulação cerebral não invasiva, tais como a estimulação magnética transcraniana repetitiva (EMTr). Embora estudos com EMTr tenham mostrado resultados promissores, poucos têm avaliado simultaneamente seus efeitos em medidas comportamentais, bioquímicas e neurofisiológicas. Assim, neste estudo avaliamos o efeito da EMTr na dor e, considerando a sua ação na função dos sistemas inibitórios corticais e intra-corticais, também investigamos parâmetros de excitabilidade cortical e níveis do mediador de neuroplasticidade BDNF, após tratamento com EMTr ou intervenção sham, em indivíduos com SDM crônica. Objetivos: Comparar o efeito de 10 sessões de EMTr ao da intervenção sham na função das vias nociceptivas cortical e subcortical (limiares de excitabilidade cortical e limiares termoalgésicos periféricos), na capacidade funcional, na qualidade do sono, nos níveis de dor, no sistema modulatório descendente de dor e nos níveis séricos de BDNF, em indivíduos com dor crônica miofascial do complexo craniocervicomaxilar. Assim, a hipótese deste estudo é que 10 sessões de EMTr, quando comparada com intervenção sham está associada com melhora nos níveis de dor, em indivíduos com dor crônica miofascial do complexo craniocervicomaxilar. Métodos: Vinte e quatro participantes do sexo feminino, com idades entre 19-65 anos, diagnosticadas com SDM do complexo craniocervicomaxilar por pelo menos 3 meses anteriores ao recrutamento e que evidenciaram componente neuropático (escore igual ou maior a quarto no DN4 – questionário para diagnóstico de dor neuropática), foram randomizadas para receber dez sessões de estimulação magnética transcraniana repetitiva (EMTr) (n = 12) de 10 Hz ou intervenção sham (n = 12). O estudo avaliou se a dor [limiares termoalgésicos (QST)], o sistema inibitório descendente [modulação condicionada da dor (QST + CPM)], a excitabilidade cortical (parâmetros da EMT) e o BDNF foram alterados após a intervenção. Resultados: Houve interação significativa (tempo versus grupo) em relação aos escores de dor, evidenciados pela escala análoga visual analógica de dor (EVA) (análise de variância, P<0,01). Análise post hoc mostrou que, em comparação com intervenção sham, o tratamento com EMTr reduziu em 30,21% os escores diários de dor (95% intervalo de confiança [IC] de -39,23 - -21,20) e em 44,56% o uso de analgésicos (-57,46 - -31,67). Comparado com o sham, o grupo que recebeu EMTr ativa aprimorou o sistema corticoespinal inibitório (redução de 41,74% no QST+CPM, P<0,05), reduziu em 23,94% a facilitação intracortical (P=0,03), aumentou em 52,02% o potencial evocado motor (P=0,02) e apresentou aumento de 12,38 ng/ml no nível sérico de BDNF (IC 95%=2,32-22,38). O grupo que recebeu EMTr demonstrou aumento na média dos escores B-PCP:S (P<0.03), redução de 45% no número de doses analgésicas diárias (P<0.003) e melhora na qualidade do sono (P<0.01). Nenhum efeito adverso foi observado. Conclusões: O tratamento com 10 sessões de EMTr de alta frequência (10 Hz) foi associado com significativa melhora na SDM crônica. EMTr reduziu os escores de dor, diminuiu o uso de analgésicos e melhorou a qualidade do sono. Os resultados do estudo também sugerem que os efeitos analgésicos da EMTr na SDM crônica foram mediados por mecanismos top-down regulation, que aumentaram a atividade do sistema corticoespinal inibitório, bem como a secreção de BDNF. / Introduction: Although the complete pathophysiology of MPS remains unknown, cumulative evidences suggest that in chronic pain the inhibitory systems are defective, as indexed by the weakening motor cortex intracortical disinhibition. The intracortical disinhibition can be partially reverted by treatment with noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS). Although rTMS studies have shown promising results, few ones have assessed simultaneously its effect on behavioral, biochemical and neurophysiological measures. Thus, this study assessed the effect of rTMS on pain and, considering its action on the function of the inhibitory cortical and intracortical systems, this trial also evaluated cortical excitability parameters and levels of a neuroplasticity mediator BDNF, after rTMS treatment or a sham intervention in patients with chronic MPS. Objectives: To compare the effect of 10 sessions of rTMS with sham intervention effects in the cortical and subcortical nociceptive pathways (cortical excitability parameters and peripheral thermoalgesic thresholds), in the functional capacity, quality of sleep, pain levels, descending pain modulatory system and in BDNF serum levels in patients with chronic myofascial pain of jaw-cranial-cervical complex. Thus, the hypothesis of this study is that 10 sessions of rTMS, when compared with sham intervention result in improvement in pain levels in subjects with chronic myofascial pain of jaw-cranial-cervical complex. Methods: Twenty-four female aged 19-65 diagnosed with MPS of jaw-cranial-cervical complex for at least three months prior to recruitment and with neuropathic pain component (score equal or higher than four in the DN4 - neuropathic pain diagnostic questionnaire) were randomized to receive ten sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). The study tested if pain [quantitative sensory testing (QST)], the descending inhibitory systems [conditioned pain modulation (QST+CPM)], the cortical excitability (TMS parameters) and the brain-derived neurotrophic factor (BDNF) have changed after intervention. Results: There was a significant interaction (time vs. group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on pain (analysis of variance, P<0.01). Post hoc analysis showed that compared with sham intervention, the treatment decreased daily pain scores by 30.21% (95% confidence interval [CI] -39.23 - -21.20) and analgesic use by 44.56 (-57.46 - -31.67). Compared to sham intervention group, the rTMS group enhanced the corticospinal inhibitory system (41.74% reduction in QST+CPM, P<0.05), decreased by 23.94% the intracortical facilitation (P=0.03), and showed an increase of 52.02% the motor evoked potential (P=0.02) and presented 12.38 ng/mL higher serum BDNF (95%CI=2.32 - 22.38). rTMS group showed an increase in mean scores B-PCP: S (P <0.03), 45% reduction in the number of daily analgesic doses (P <0.003) and significantly better sleep quality (P <0.01). No adverse event was observed. Conclusions: The treatment with 10 sessions of high-frequency rTMS (10 Hz) was associated with significant improvement in chronic MPS. rTMS reduced pain scores, lowered analgesic use and improved sleep quality. The results also suggested that the rTMS analgesic effects in chronic MPS were mediated by top-down regulation mechanisms enhancing the activity of the corticospinal inhibitory system and that this effect involved an increase in BDNF secretion.

Introdução: Embora a completa fisiopatologia da SDM permaneça desconhecida, evidências sugerem que na dor crônica os sistemas inibitórios são deficitários, como demonstrado pelo enfraquecimento da inibição intracortical do córtex motor. No entanto, a desinibição intracortical pode ser parcialmente revertida pelo tratamento com técnicas de estimulação cerebral não invasiva, tais como a estimulação magnética transcraniana repetitiva (EMTr). Embora estudos com EMTr tenham mostrado resultados promissores, poucos têm avaliado simultaneamente seus efeitos em medidas comportamentais, bioquímicas e neurofisiológicas. Assim, neste estudo avaliamos o efeito da EMTr na dor e, considerando a sua ação na função dos sistemas inibitórios corticais e intra-corticais, também investigamos parâmetros de excitabilidade cortical e níveis do mediador de neuroplasticidade BDNF, após tratamento com EMTr ou intervenção sham, em indivíduos com SDM crônica. Objetivos: Comparar o efeito de 10 sessões de EMTr ao da intervenção sham na função das vias nociceptivas cortical e subcortical (limiares de excitabilidade cortical e limiares termoalgésicos periféricos), na capacidade funcional, na qualidade do sono, nos níveis de dor, no sistema modulatório descendente de dor e nos níveis séricos de BDNF, em indivíduos com dor crônica miofascial do complexo craniocervicomaxilar. Assim, a hipótese deste estudo é que 10 sessões de EMTr, quando comparada com intervenção sham está associada com melhora nos níveis de dor, em indivíduos com dor crônica miofascial do complexo craniocervicomaxilar. Métodos: Vinte e quatro participantes do sexo feminino, com idades entre 19-65 anos, diagnosticadas com SDM do complexo craniocervicomaxilar por pelo menos 3 meses anteriores ao recrutamento e que evidenciaram componente neuropático (escore igual ou maior a quarto no DN4 – questionário para diagnóstico de dor neuropática), foram randomizadas para receber dez sessões de estimulação magnética transcraniana repetitiva (EMTr) (n = 12) de 10 Hz ou intervenção sham (n = 12). O estudo avaliou se a dor [limiares termoalgésicos (QST)], o sistema inibitório descendente [modulação condicionada da dor (QST + CPM)], a excitabilidade cortical (parâmetros da EMT) e o BDNF foram alterados após a intervenção. Resultados: Houve interação significativa (tempo versus grupo) em relação aos escores de dor, evidenciados pela escala análoga visual analógica de dor (EVA) (análise de variância, P<0,01). Análise post hoc mostrou que, em comparação com intervenção sham, o tratamento com EMTr reduziu em 30,21% os escores diários de dor (95% intervalo de confiança [IC] de -39,23 - -21,20) e em 44,56% o uso de analgésicos (-57,46 - -31,67). Comparado com o sham, o grupo que recebeu EMTr ativa aprimorou o sistema corticoespinal inibitório (redução de 41,74% no QST+CPM, P<0,05), reduziu em 23,94% a facilitação intracortical (P=0,03), aumentou em 52,02% o potencial evocado motor (P=0,02) e apresentou aumento de 12,38 ng/ml no nível sérico de BDNF (IC 95%=2,32-22,38). O grupo que recebeu EMTr demonstrou aumento na média dos escores B-PCP:S (P<0.03), redução de 45% no número de doses analgésicas diárias (P<0.003) e melhora na qualidade do sono (P<0.01). Nenhum efeito adverso foi observado. Conclusões: O tratamento com 10 sessões de EMTr de alta frequência (10 Hz) foi associado com significativa melhora na SDM crônica. EMTr reduziu os escores de dor, diminuiu o uso de analgésicos e melhorou a qualidade do sono. Os resultados do estudo também sugerem que os efeitos analgésicos da EMTr na SDM crônica foram mediados por mecanismos top-down regulation, que aumentaram a atividade do sistema corticoespinal inibitório, bem como a secreção de BDNF. / Introduction: Although the complete pathophysiology of MPS remains unknown, cumulative evidences suggest that in chronic pain the inhibitory systems are defective, as indexed by the weakening motor cortex intracortical disinhibition. The intracortical disinhibition can be partially reverted by treatment with noninvasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS). Although rTMS studies have shown promising results, few ones have assessed simultaneously its effect on behavioral, biochemical and neurophysiological measures. Thus, this study assessed the effect of rTMS on pain and, considering its action on the function of the inhibitory cortical and intracortical systems, this trial also evaluated cortical excitability parameters and levels of a neuroplasticity mediator BDNF, after rTMS treatment or a sham intervention in patients with chronic MPS. Objectives: To compare the effect of 10 sessions of rTMS with sham intervention effects in the cortical and subcortical nociceptive pathways (cortical excitability parameters and peripheral thermoalgesic thresholds), in the functional capacity, quality of sleep, pain levels, descending pain modulatory system and in BDNF serum levels in patients with chronic myofascial pain of jaw-cranial-cervical complex. Thus, the hypothesis of this study is that 10 sessions of rTMS, when compared with sham intervention result in improvement in pain levels in subjects with chronic myofascial pain of jaw-cranial-cervical complex. Methods: Twenty-four female aged 19-65 diagnosed with MPS of jaw-cranial-cervical complex for at least three months prior to recruitment and with neuropathic pain component (score equal or higher than four in the DN4 - neuropathic pain diagnostic questionnaire) were randomized to receive ten sessions of repetitive transcranial magnetic stimulation (rTMS) (n = 12) at 10 Hz or a sham intervention (n = 12). The study tested if pain [quantitative sensory testing (QST)], the descending inhibitory systems [conditioned pain modulation (QST+CPM)], the cortical excitability (TMS parameters) and the brain-derived neurotrophic factor (BDNF) have changed after intervention. Results: There was a significant interaction (time vs. group) regarding the main outcomes of the pain scores as indexed by the visual analogue scale on pain (analysis of variance, P<0.01). Post hoc analysis showed that compared with sham intervention, the treatment decreased daily pain scores by 30.21% (95% confidence interval [CI] -39.23 - -21.20) and analgesic use by 44.56 (-57.46 - -31.67). Compared to sham intervention group, the rTMS group enhanced the corticospinal inhibitory system (41.74% reduction in QST+CPM, P<0.05), decreased by 23.94% the intracortical facilitation (P=0.03), and showed an increase of 52.02% the motor evoked potential (P=0.02) and presented 12.38 ng/mL higher serum BDNF (95%CI=2.32 - 22.38). rTMS group showed an increase in mean scores B-PCP: S (P <0.03), 45% reduction in the number of daily analgesic doses (P <0.003) and significantly better sleep quality (P <0.01). No adverse event was observed. Conclusions: The treatment with 10 sessions of high-frequency rTMS (10 Hz) was associated with significant improvement in chronic MPS. rTMS reduced pain scores, lowered analgesic use and improved sleep quality. The results also suggested that the rTMS analgesic effects in chronic MPS were mediated by top-down regulation mechanisms enhancing the activity of the corticospinal inhibitory system and that this effect involved an increase in BDNF secretion.