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Orientador: Maria Cláudia Gonçalves de Oliveira Fusaro / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Aplicadas / Made available in DSpace on 2018-08-25T13:05:07Z (GMT). No. of bitstreams: 1 Melo_Brunade_M.pdf: 1160481 bytes, checksum: cafc4360aa16080c8eb0784f74e162b8 (MD5) Previous issue date: 2014 / Resumo: Estudos demonstram que a dor muscular induzida por contração isométrica sustentada (CIS) possui importante impacto socioeconômico, no entanto, apesar de sua relevância clínica, os mecanismos inflamatórios envolvidos no desenvolvimento desse tipo de dor ainda são pouco compreendidos. O objetivo deste estudo foi analisar os mecanismos inflamatórios envolvidos no desenvolvimento desse tipo de hiperalgesia muscular. Para isso foi utilizado o modelo de hiperalgesia muscular induzido por contração isométrica sustentada, recentemente desenvolvido por nosso grupo de pesquisa, que consiste na indução de contração muscular isométrica no músculo gastrocnêmio de ratos machos Wistar, pesando entre 200 e 250g, que receberam uma corrente elétrica através do equipamento da marca Grass, modelo SX88R, corrente monofásica, pulso repetido, frequência de 50Hz, duração de pulso de 19ms através de eletrodos tipo agulha, pelo período de 1 hora. Para traçar o perfil inflamatório deste modelo foram administrados via intramuscular, 5 minutos, antes da contração isométrica as seguintes drogas: DALB K (3;30'mu'g) e Bradizida (1,5;15 'mu'g)(antagonistas dos receptores de bradicinina B1 e B2, respectivamente), Atenolol (0,6; 6'mu'g) e ICI 118551(0,15;1,5'mu'g) (antagonistas dos receptores adrenérgicos 'beta'1 e 'beta', respectivamente), Indometacina, uma hora antes (10;100'mu'g) (inibidor não seletivo das cicloxigenases) e A317491 (0,6; 6; 60 'mug) (antagonista seletivo dos receptores P2X3 e P2X2/3); e administrado intraperitoneal, 20 minutos antes, a Fucoidina (25mg/Kg) (inibidora da ação das selectinas). Os resultados demonstraram que todos esses antagonistas e inibidores reduziram significativamente a hiperalgesia muscular induzida pela contração isométrica sustentada, confirmando o envolvimento da bradicinina, aminas simpatomiméticas, prostaglandinas, neutrófilos e do ATP endógeno via receptores P2X3 e P2X2/3 na hiperalgesia muscular induzida pela contração isométrica sustentada. Esses resultados delineiam pela primeira vez o perfil inflamatório da hiperalgesia muscular induzida por contração isométrica sustentada e sugerem importantes alvos terapêuticos para estudo e tratamento da dor muscular, além de abrir novas perspectivas de estudo de outros mecanismos importantes no desenvolvimento da mesma / Abstract: Studies show that muscle pain induced by sustained isometric contraction (CIS) have an important socioeconomic impact, however, despite their clinical relevance, the inflammatory mechanisms involved in the development of this type of pain are still poorly understood. The aim of this study was to analyze the inflammatory mechanisms involved in the development of this type of muscle hyperalgesia. For this model of muscle hyperalgesia induced by sustained isometric contraction, recently developed by our research group, which consists of the induction of isometric muscle contraction in the gastrocnemius muscle of male Wistar rats were used, weighing between 200 and 250g, receiving an electric current through the equipment brand Grass , model SX88R , single phase , repeated pulse frequency of 50 Hz , pulse duration of 19ms via needle-like electrodes for a period of 1 hour. To trace the inflammatory profile of this model, the following drugs were administered intramuscularly 5 minutes before the isometric contraction: DALB K (3; 30'mu'g) and Bradizyde (1.5, 15 mg) (antagonists of bradykinin B1 and B2 receptors, respectively), Atenolol (0.6 ; 6'mu'g) and ICI 118551 (0.15, 1.5 mg) ('beta1 and 'beta'2 adrenergic receptor antagonists, respectively), indomethacin (10 ; 100'mu'g ) ( inhibitory action of cyclooxygenase ) and A317491 ( 0.6 , 6, 60 mg) (selective antagonist of P2X3 and P2X2 / 3 receptors) , and administered intraperitoneally 20 minutes before the fucoidin ( 25mg/Kg ) ( inhibitory action of selectins) . The results showed that all of these antagonists and inhibitors significantly reduced muscular hyperalgesia induced by sustained isometric contraction, confirming the involvement of bradykinin, sympathomimetic amines, prostaglandins, neutrophils and endogenous ATP via P2X3 and P2X2/3 receptors in muscle hyperalgesia induced by isometric contraction sustained. These results delineate first the inflammatory profile of muscle hyperalgesia induced by sustained isometric contraction and suggest important targets for study and treatment of muscle pain, and open new perspectives for the study of other important mechanisms in the development of the same / Mestrado / Biodinâmica do Movimento Humano e Esporte / Mestra em Ciências da Nutrição e do Esporte e Metabolismo

Stress can be defined as feelings of frustration or anxiety that arise when individuals face challenges that exceed their capabilities or resources. Consequences of stress generally result from a suppressed immune system and include headaches, sleep problems, and muscle pain. Music as an intervention for relieving pain has increased due to its non-invasive nature, ease of administration, low cost, and lack of adverse side effects. While prior research on music therapy and pain has primarily focused on pain related to surgery, disease, or accidents, there have been no studies to date examining the association between music therapy and stress-induced muscle pain. I have designed a study proposal to establish the relationship between music therapy and muscle pain related to stress. The proposed study will compare salivary cortisol levels, pain visual analogue scale (VAS) scores, the number of painkillers consumed, and the number of doctor visits of healthy individuals experiencing the same stressor (MCAT or GRE) over a 3 month period. One group of participants will be randomly assigned to listen to an additional 30 minutes of self-chosen calming music a day, whereas the other will not listen to any additional music. It is hypothesized that the participants that listen to the additional calming music will experience significantly lower levels of stress and therefore lower muscle pain levels than the participants that did not listen to music. This research is potentially useful for students who undergo constant stress due to the demands of college. Future studies could include whether music therapy allows students to study longer by relieving some of the muscle pain caused by stress.

Embora as causas de DTM tenham sido muito estudadas e discutidas na literatura atual, a associação entre a dor muscular e sua temperatura não está totalmente clara. Para esta investigação, 40 pacientes com dor muscular foram encaminhados da clínica odontológica e foram examinados. Um total de 31 pacientes foram diagnosticados com dor miofascial no musculo masseter pelo RDC e foram incluídos neste estudo. O musculo masseter no lado com dor foi anestesiado e foi comparado ao lado oposto ao longo do tempo. Na análise estatística de comparação, foi encontrada associação entre o aumento de temperatura e a diminuição da dor relatada. Possíveis fatores de confusão, como tempo da dor crônica, idade, índice de massa corpórea, pontos de incapacidade, ICD, pior dor sentida nos últimos meses e dor media nos últimos meses foram levados em consideração e foram estatisticamente analisados e o único fator que mostrou estatisticamente correlação com a diminuição da dor foi o fator tempo. Conclusão: existe uma correlação negativa entre o aumento de temperatura e a diminuição da dor. / Although, TMD causes have been widely studied in the last years, the association between muscle pain and temperature remains unclear. For this investigation, 40 muscle pain patients were referred from dental clinic and were examined. A total of 31 patients were diagnosed with masseter myofascial pain by RDC criteria and were included in this study. Masseter muscle was blocked in the pain side and was compared among the time to opposite side. In the matching statistics association analysis, it was found association between temperature increase and related pain decrease. Possible confounders (time of chronic pain, age, Body Mass Index, ICD, incapacity points, worst pain in the last six months, average pain in last six month) were took in consideration and only time since the pain started seems to be related to decrease in pain. Conclusion: there is a negative association between muscle pain and muscle temperature.

Afecções musculoesqueléticas crônicas são um problema de saúde pública devido à sua alta prevalência, seu alto custo econômico e por seu impacto negativo na qualidade de vida de pacientes e seus familiares. Diante disso, pesquisadores têm estudado lesões musculares em modelos animais para melhor compreensão dos mecanismos envolvidos na iniciação e manutenção de distúrbios musculoesqueléticos. Na tentativa de esclarecer os mecanismos nociceptivos envolvidos neste processo e encontrar terapias efetivas, nosso grupo de pesquisa vem utilizando modelos experimentais de dor e potenciais tratamentos farmacológicos e não farmacológicos como objeto de estudo. O presente estudo teve como finalidade avaliar se o tratamento farmacológico com gabapentina é eficaz em reverter a dor muscular de ratos com miosite crônica induzida pela injeção de Adjuvante de Freund Completo (CFA) no músculo gastrocnêmio, e ainda, analisar a influência da gabapentina em células gliais e citocinas pró e anti-inflamatórias no sistema nervoso central e periférico destes animais. Nossos resultados demonstram o efeito da gabapentina em células gliais. Esta ação induz uma diminuição na expressão de astrócitos e microglias, levando a um aumento de citocinas anti-inflamatórias e inibição de citocinas pró-inflamatórias e consequentemente uma melhora do quadro nociceptivo em nosso modelo experimental. / Chronic musculoskeletal disorders are a public health problem due to its high prevalence, high economic cost and negative impact on patients and their relatives quality of life. Due to this, researchers have been studying muscle injury in animal models to better understand the mechanisms involved in the initiation and maintenance of musculoskeletal disturbs. To elucidate the nociceptive mechanisms involved in this process and seek for effective therapies, our research group has been using experimental models of pain and potential pharmacological and non-pharmacological treatments as object of study. The aim of this study was to assess whether the treatment with gabapentin is effective in reversing the muscle pain injury in rats with chronic myositis induced by the injection of Complete Freund\'s Adjuvant (CFA) in the gastrocnemius muscle. Also to analyze the influence of gabapentin on glial cells and pro-and anti-inflammatory cytokines in the central and peripheral nervous system of these animals. Our results demonstrate the effect of gabapentin on glial cells. This action are able to decrease expression of astrocytes and microglia, leadind to an increase in anti-inflammatory cytokines and inhibition of proinflammatory cytokines and an improvement of the nociceptive picture in our experimental mode.

Computer technology has advanced rapidly in the past few decades and computers have become a very important and powerful tool in our everyday lives. Prolonged computer use by office workers has been reported to result in an increased risk of developing Work-related Neck and Upper Limb Disorders (WRNULD) (Bernard et al.. 1994: Faucett & Rempel. 1994: Tittiranonda et al.. 1999). The occupational risk factors associated with prolonged computer use include static posture and the speed and force of keyboard operation. Past studies have examined different aspects of these risk factors through measuring muscle electrical activity (EMG), kinematics and keyboard forces. However, most of these studies have been conducted on healthy painfree subjects and even the few Case-Control studies have not clearly established any direct relationships between the risk factors and WRNULD. The present research project consisted of a series of three studies aimed at investigating whether there were intrinsic differences among different individuals in response to different physical stressors. These intrinsic differences may have important implications to help explain why some individuals would develop WRNULD while others do not. The individuals' responses to the demands of three physical stressors: static posture, speed and force of keyboard operation were assessed. The internal exposure measures of kinematics, EMG, keyboard dynamics and subjective discomforts were used to evaluate the inter-individual differences. Study I was a field investigation comparing the neck-shoulder kinematics between symptomatic ("Case", n=8) and asymptomatic ("Control", n=8) office workers. Results showed trends for consistently greater head tilt and neck flexion angles, and greater ranges of movements in the Case Group than the Control Group. / The Case Group also exhibited a trend for increased acromion protraction compared to the Control Group. The Case Group also reported significantly greater discomfort scores compared to the Control Group. Neither the discomforts nor the kinematics displayed any significant changes over a working day. Study 2 was a laboratory study comparing the responses of Case and Control Groups in terms of EMG, kinematics and subjective discomforts, while a standardised computer task was performed continuously for one hour. The responses of Case (n=23) and Control (n=20) Groups were compared to examine the effects of static posture. The results showed similar trends to those in Study I, with increased neck flexion mean angles and ranges of movements in the Case Group compared to the Control Group. In terms of EMG results, there were trends for EMG amplitude differences in the right upper trapezius (UT) and cervical erector spinae (CES) muscles between Case and Control Groups. These trends became statistically significant when the Case subjects were sub-divided into the High (n=15) and Low (n=8) Groups based on their mean discomfort scores. Study 3 was also a laboratory study to compare the Case (n=21) and Control (n=20) Groups when they were challenged by the physical stressors of speed and force of keyboard operation. In this study, each subject's EMG and discomforts were examined in three typing conditions of normal speed and force, increased typing speed and increased typing force. The Case Group showed trends for higher increases in both UT and CES muscle activities than the Control Group, and when divided into the High-Low Groups, the High Group (n=8) showed trends for much higher muscle activities in all three conditions. / Beside muscle activity changes, the High Group subjects also demonstrated a trend for much higher within-subject Speed and Force Variabilities in their keystroke performance, compared to the Low Group and the Control Group. This result implied that the High Group subjects had a more erratic motor control of the keystroke actions. Based on these results, conceptual models were developed to describe the relationships among the physical stressors, internal exposure responses and discomforts. The Altered Motor Control Model refers to the programmed changes in motor control strategies involving muscle recruitment and joint movement patterns, and these changes were closely related to the subjects' musculoskeletal discomforts. The Heightened Sensitivity Model describes the higher sensitivity levels of individuals with more severe discomforts, in response to the demands of physical stressors. These models are closely related and heightened sensitivity may be an 'effect-modifier" of the motor control mechanisms and the perception of discomforts or pains within the individual. In conclusion, the present research has identified important differences between individuals on the basis of their motor control strategies which may contribute to the development of WRNULD. While the present research has mainly examined the individual responses to three physical stressors, it is possible that the models developed may be applicable to other physical stressors. These findings may also have important implications for future ergonomic research, emphasising the need to address interindividual differences in ergonomic interventions to workers. Further research should be directed towards better understanding of these intrinsic individual differences in both physical and non-physical factors that contribute to the development of WRNULD.

Low-load repetitive work (LLRW) and mental load are important risk factors for the development of workrelated muscle pain. The link between these risk factors and the development of pain is still not understood, but stimulation of chemo-sensitive receptors in the muscle probably plays an important role. It has been suggested that sensitising substances may accumulate in the muscle during LLRW, especially when combined with mental load. The overall purpose of this thesis was to try to shed some light on the effects of LLRW on the concentration of sensitising substances (glutamate, prostaglandin E2 (PGE2), norepinephrine (NE)) and on metabolism (lactate, pyruvate and oxygenation) in the trapezius muscle of healthy controls (CON) and subjects with trapezius myalgia (TM). A first step was to investigate whether females with TM exhibit higher absolute concentrations of glutamate and PGE2 in the affected muscle during rest. Using Microdialysis (MD) females with TM and asymptomatic controls were studied during four hours of rest. [Glutamate] and [PGE2] during rest did not differ between groups. A second step was to investigate, in a simulated occupational setting, the effects of LLRW on the concentration of sensitising substances and metabolism in the trapezius muscle of TM and CON, and whether increased work duration resulted in a progressive effect. Asymptomatic females were studied during baseline rest, 30 versus 60 min work and recovery, using MD and near infrared spectroscopy (NIRS). Subjects with TM were studied during baseline rest, 30 min work and recovery. [Glutamate] and [lactate] increased in response to work, but not progressively with increased work duration. [Glutamate] was at all time points significantly lower in TM. [PGE2]and oxygenation remained unchanged during work for CON, while for TM oxygenation decreased significantly during work. In TM [pyruvate] increased during both work and recovery, and a significant interaction between groups was found for [pyruvate] during recovery; while moderately increased in CON it increased progressively in TM. The effects of LLRW with and without superimposed mental load on intramuscular [NE], muscle activity and oxygen saturation in the trapezius were also investigated and compared. Using MD, electromyography and NIRS, healthy females were studied on two occasions; during 30 min LLRW and during 30 min LLRW with superimposed mental load. During work [NE], and muscle activity, were increased, while oxygenation decreased, but no differences between occasions. However, recovery of [NE] to baseline was slower after LLRW with superimposed mental load. The findings of the present thesis suggest: (i) no inflammation, or increased interstitial [glutamate] in TM; (ii) LLRW causes an increased anaerobic metabolism in both TM and CON; (iii) no effect of work duration was found; (iv) a significant difference in the effects of LLRW on the interstitial milieu of the trapezius muscle in TM as compared to CON; (v) LLRW causes a significant increase in [NE], but superimposed mental load does not cause a further increase; (vi) LLRW with a superimposed mental load may result in a slower recovery to baseline [NE] as compared with LLRW alone.

In the early nineties cannabinoid receptors, the main target for Δ9-tetrahydrocannabinol (THC), the psychoactive component of marijuana were identified. Shortly after their endogenous ligands, N-arachidonoylethanolamine (anandamide, AEA) and 2-diacylglycerol (2-AG) were characterized. The enzymes primarily responsible for catalysing the degradation of AEA and 2-AG are fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL) respectively. AEA is a member of the N-acylethanolamine (NAE) class of lipids, which depending on the acyl chain length and number of double bonds can act as ligands for a variety of biological targets. Exogenous cannabinoids have long been reported to have analgesic effects, however the clinical usefulness of such substances is limited by their psychoactive effects. Inhibition of endocannabinoid degradation would mean enhancing the therapeutic effects without producing these unwanted side effects. In order to succeed in developing such compounds the pharmacology of the enzymes responsible for the degradation of endocannabinoids has to be thoroughly understood. When the preclinical part of this thesis was planned, FAAH had been well characterized whereas little was known as to the pharmacology of MGL. A series of compounds were tested in this first study aiming to find MGL-selective compounds. Although no compounds showed selectivity for MGL over FAAH, several interesting agents affecting both enzymes were identified. In order to increase the knowledge concerning which patient group would benefit from such treatment strategies it is important to investigate in which pain states the endocannabinoids/NAEs are altered. Thus the general aim of the clinical part of this thesis was to investigate the levels of endocannabinoids/NAEs in the interstitium of the trapezius muscle in women suffering from chronic neck/shoulder pain (CNSP) and chronic wide spread pain (CWP) and in healthy pain-free controls. Furthermore for the CNSP the effect of training, which is a commonly recommended treatment for these patients, on the levels of endocannabinoids/NAEs was also investigated. Microdialysis technique in the trapezius muscle was used for sampling and masspectrometry was used for analysing. Two NAEs, N-palmitoylethanolamine (PEA) and N-stearoylethanolamine (SEA), could be repeatedly measured. The levels of these two lipids were significantly higher in CNSP compared to CON. The result showed also that PEA and SEA mobilize differently in CWP compared to both CNSP and CON. Taken together the results presented in thesis represent an early characterization of the pharmacology of MGL and provides novel information on NAEs in chronic muscle pain.

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Embora as causas de DTM tenham sido muito estudadas e discutidas na literatura atual, a associação entre a dor muscular e sua temperatura não está totalmente clara. Para esta investigação, 40 pacientes com dor muscular foram encaminhados da clínica odontológica e foram examinados. Um total de 31 pacientes foram diagnosticados com dor miofascial no musculo masseter pelo RDC e foram incluídos neste estudo. O musculo masseter no lado com dor foi anestesiado e foi comparado ao lado oposto ao longo do tempo. Na análise estatística de comparação, foi encontrada associação entre o aumento de temperatura e a diminuição da dor relatada. Possíveis fatores de confusão, como tempo da dor crônica, idade, índice de massa corpórea, pontos de incapacidade, ICD, pior dor sentida nos últimos meses e dor media nos últimos meses foram levados em consideração e foram estatisticamente analisados e o único fator que mostrou estatisticamente correlação com a diminuição da dor foi o fator tempo. Conclusão: existe uma correlação negativa entre o aumento de temperatura e a diminuição da dor. / Although, TMD causes have been widely studied in the last years, the association between muscle pain and temperature remains unclear. For this investigation, 40 muscle pain patients were referred from dental clinic and were examined. A total of 31 patients were diagnosed with masseter myofascial pain by RDC criteria and were included in this study. Masseter muscle was blocked in the pain side and was compared among the time to opposite side. In the matching statistics association analysis, it was found association between temperature increase and related pain decrease. Possible confounders (time of chronic pain, age, Body Mass Index, ICD, incapacity points, worst pain in the last six months, average pain in last six month) were took in consideration and only time since the pain started seems to be related to decrease in pain. Conclusion: there is a negative association between muscle pain and muscle temperature.