This dissertation presents three experiments designed to demonstrate the effects of cognitive, emotional and psychosocial factors on pain perception in humans and to identify potential neuroanatomical substrates of attentional and emotional pain modulation. / The first two chapters provide an introduction, including the statement of the rationale and objectives of this Ph.D. project (Chapter 1) and an overview of the relevant background literature (Chapter 2). / Chapter 3 presents a voxel-based morphometry study on the neural correlates of attentional and emotional pain modulation. In agreement with the observation that manipulations of emotion and attention differentially affect pain perception, the results of this experiment suggest that separate neuroanatomical substrates may underlie these pain modulations: the right lateral orbitofrontal, left medial prefrontal, and bilateral entorhinal cortices appear to be implicated in emotional pain modulation, while the right putamen appears to be involved in attentional pain modulation. / The study described in Chapter 4 shows that the experimental manipulation of mood using emotionally-laden visual stimuli preferentially alters pain unpleasantness, leaving pain intensity unaffected. This study replicates the psychophysical observations presented in the study of Chapter 3 (and in previous reports), which used odors to manipulate emotional state, therefore suggesting the independence of this phenomenon from the mood induction technique employed. / The study in Chapter 5 shows that empathy has an effect on pain perception as well, which cannot be explained by mood effects. Participants for whom a state of high empathy was evoked rated painful stimuli applied to themselves as more intense and unpleasant than did those in a state of low empathy; furthermore, the state empathy ratings correlated with the pain ratings. / By showing that emotional state, attention and empathy can influence pain perception, the work in this thesis provides evidence demonstrating that the pain experience can be significantly molded by top-down factors, and is therefore far from being solely determined by the physical properties of the noxious stimulation. These observations might partially explain why the pain response in certain situations appears disproportionately large, or surprisingly small, in relation to the noxious stimulation, and support the utility of psychological methods in the management of pain symptoms.

Chronic pain patients have poorer pain inhibition, self-regulatory ability, executive functioning and autonomic inhibition than those without pain, supporting the view that suppressing pain is mentally taxing. In the current study, an alternate explanation was proposed; namely, that pain inhibition, self-regulation, executive functions, and heart rate variability (HRV) are all controlled by the same general inhibitory system. To test this hypothesis, participants came into the laboratory for three sessions. At the first session, individual differences in pain thresholds, self-regulatory strength, executive functioning, and HRV were measured. At the second and third sessions, self-regulatory persistence and within-session changes in pain thresholds were measured under conditions of high and low self-regulatory fatigue. Results revealed that those low in inhibitory strength, operationalized as the aggregate of pain inhibition, self-regulation, executive functioning, and HRV, became more sensitive to pain under conditions of self-regulatory fatigue, whereas no significant changes in pain threshold were found for those high in inhibitory strength. Additional analyses revealed that high baseline pain threshold marginally protected against the effects of self-regulatory fatigue. The findings provide some support for a general inhibitory system and suggest that physiological inhibition of pain and autonomic activity may be influenced by phasic self-regulatory fatigue.

Non-Suicidal Self-Injury (NSSI) is the self-inflicted damage to one’s bodily tissues without the intent to die. Previous research has sought to discover the motivation of an individual to perform such behavior and differences in the experience of pain among those who self-injure. The goals for the current study were to reveal any relationships between the function of NSSI, the subjective experience of pain, and an objective measurement of pressure pain threshold. Participants completed the Inventory of Statements About Self- Injury (ISAS; Klonsky & Glenn, 2009), which measures the functions that NSSI serves, and a measure assessing subjective pain experience, specifically frequency and severity of pain. Pain thresholds were also induced and recorded using a pressure algometer. The findings suggest that pain frequency significantly predicted pain threshold, whereas subjective pain severity did not. Furthermore, marking distress, the function of NSSI which serves as creating a tangible representation of emotional distress, was significantly associated with pain frequency, such that as marking distress increases in relevance, the less often one would be expected to experience pain. Therefore, the current study has implications relevant to both future research and the clinical setting.

国立情報学研究所で電子化したコンテンツを使用している。

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Cenário clínico: A síndrome dolorosa miofascial (SDM), causa comum de dor musculoesquelética, pode ser incapacitante e desafiadora terapeuticamente, devido à ineficácia dos tratamentos convencionais para dor. Intervenções terapêuticas alternativas precisam ser pesquisadas para alcançar vias do processo de doença não contempladas com a terapêutica clássica. Dentre estas, o uso da melatonina, com efeitos cronobiótico, ansiolítico e analgésico, tem se apresentado como uma opção terapêutica atrativa no tratamento da SDM, que cursa com alterações de sono, dor, sintomas depressivos e de ansiedade. Objetivos: Avaliar a eficácia da melatonina exógena na redução da dor, no limiar de dor à pressão (LDP) e na qualidade de sono de pacientes com SDM facial. Métodos e Resultados: Um estudo randomizado, controlado foi realizado em 45 mulheres com dor miofascial, com idades entre 18 e 40 anos, segundo critérios Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD). A eficácia da melatonina oral foi avaliada na redução da dor e melhora tanto do limiar de dor a pressão (LDP) como da qualidade do sono. Os participantes foram randomizados para receber 5 mg / dia de melatonina, 5 mg / dia ciclobenzaprina, ou placebo durante um período de quatro semanas. O efeito absoluto das intervenções, apresentado como ES (tamanho do efeito) sobre a dor: placebo versus melatonina foi de 2,08 (1,17-2,97) e de ciclobenzaprina vs placebo foi de -1,25 (0,45-2,06)]. O número de pacientes necessários para tratar (NNT) para evitar a dor moderada a intensa foi 3 (95% CI, 2-4) e 18 (95% IC, 9 a a) nos grupos de melatonina e de ciclobenzaprina, respectivamente, em relação ao placebo. O ES no LDP melatonina vs placebo e ciclobenzaprina vs placebo foi de 2,72 (1,69-3,75) e 1,01 (0,23-1,79), respectivamente. O ES na escala visual analógica de Qualidade de Sono (VASQS) utilizada para avaliar a forma como as pacientes se sentiram ao acordar, durante o período de tratamento, foi nos grupos melatonina versus placebo de 2,47 (1,49-3,45) e 1,01 (0,23-1,79), respectivamente. Conclusão: Melatonina foi mais eficaz do que placebo para melhorar a dor miofascial crônica facial e ambos os tratamentos foram mais eficazes do que placebo para melhorar o LDP e a qualidade de sono. / Background: The Myofascial Pain Syndrome (SDM), a common cause of musculoskeletal pain, can course with disability and can be a therapeutical challenge, due to the ineffectiveness of conventional treatments for pain. Alternative therapeutic interventions must be researched to achieve the process of the disease process that in not dealt with the classical therapy. Among these, the use of melatonin, which takes effect chronobiotic, anxiolytic and analgesic, has been presented as an attractive therapeutic option in the treatment of SDM, which leads to sleep disturbances, pain, anxiety and depressive symptoms. Objectives: Evaluate the efficacy of exogenous melatonin in reducing pain, pain pressure threshold (PPT) and the sleep quality of patients with chronic myofascial face pain. Methods and Results: A randomized, controlled trial was conducted with 45 females, aged 18 to 40 years who presented myofascial pain according to the Research Diagnostic Criteria for Temporomandibular Disorder (RDC/TMD) guidelines. The efficacy of oral melatonin was evaluated in reducing pain and improving both the pain pressure threshold (PPT) and sleep quality. Participants were randomized to receive 5 mg/day melatonin, 5 mg/day cyclobenzaprine, or a placebo during a four-week period. The absolute effect of interventions, presented as ES (effect size) on pain for melatonin vs. placebo was 2.08 (1.17 to 2.97) and for cyclobenzaprine vs. placebo -1.25 (0.45 to 2.06)], respectively. The Number of Patients Needed to be Treated (NNT) to prevent moderate to intense pain was 3 (95% CI, 2 to 4) and 18 (95% CI, 9 to ) in the melatonin and cyclobenzaprine groups, respectively compared to the placebo. The ES on the PPT for melatonin vs. placebo and cyclobenzaprine vs. placebo was 2.72 (1.69 to 3.75) and 1.01 (0.23 to 1.79), respectively. The ES on the Visual Analog Sleep Quality Scale (VASQS) scores used to assess how they felt when they woke up during the treatment period for the melatonin vs. placebo were 2.47 (1.49 to 3.45) and 1.01 (0.23 to 1.79), respectively. Conclusion: Melatonin was more effective than placebo for improving chronic myofascial face pain and both treatments were more effective than placebo for improving sleep quality and the PPT.

Introdução: Embora a relação entre privação de sono e limiar de dor tenha sido estudada em condições patológicas de quadros álgicos agudos e crônicos, os mecanismos envolvidos neste processo ainda carecem de investigações. Nesse contexto, sabe-se que são crescentes as situações nas quais a restrição de sono aguda é induzida por atividades laborais cotidianas, e a compreensão desta relação demanda modelos que permitam observar o efeito em condições em que os estímulos sejam padronizados e controlados. Assim sendo, investigamos o efeito da restrição aguda de sono na função autonômica e sua relação com limiares de dor em indivíduos saudáveis. Objetivos: Avaliar a relação entre respostas autonômicas e percepção a estímulos nociceptivos térmicos e elétricos pós-restrição aguda de sono ocasionada por estresse laboral. Métodos: Foram avaliados 19 estudantes de Medicina saudáveis após noite de sono habitual (SN) e após plantão noturno de 12 horas (RS). Primeiramente examinamos características clínicas dos sujeitos utilizando escalas para avaliação de sono e sintomas psiquiátricos. Foram realizados também testes quantitativos de sensibilidade para sensações térmicas e elétricas e registradas respostas cutâneas simpáticas (RCS) induzidas por estímulo elétrico duplo com diferentes intervalos interestímulos (ISI). Resultados: A média de duração do sono durante as 12 horas de plantão noturno foi de 120+ 28 minutos. Os escores de ansiedade foram maiores na fase RS quando comparados com os da fase SN (p<0,01). Após restrição de sono, houve diminuição no limiar de dor, mas não nos limiares de calor e elétricos. Em relação às respostas autonômicas, foram evidenciadas maiores amplitudes da RCS bem como aumento do número de duplas respostas em ISI 2s na fase RS. Também foi observada moderada correlação inversa entre limiares de dor e amplitudes da RCS (r= -0,45; p<0,01). Não foi encontrada correlação entre escores de ansiedade e parâmetros RCS. No entanto, no modelo de regressão linear multivariada, a percepção do limiar de dor ao estímulo térmico foi significativamente correlacionada com a amplitude da resposta cutânea simpática (β = - 0.55; 95% CI, -0.65 to -0.07), mas não com escores de ansiedade (p>0.05). Conclusões: Os efeitos da restrição aguda de sono no limar de dor são específicos e parecem não estar relacionados com alterações na percepção sensorial geral. Hiperalgesia foi associada com respostas autonômicas anormais, mas não com aumento da ansiedade, sugerindo a existência de uma associação entre o sistema nociceptivo e o autonômico, independente do estado emocional. / Background: Although the relationship between sleep deprivation and pain threshold has been studied in pathological acute and chronic conditions, the mechanisms involved in this process still require investigation. In this context, it is known that there is an increasing of situations where acute sleep restriction is induced by daily working activities and to understand this relationship is necessary models that allow the observation of the effect in situations in which the stimuli are standardized and controlled. Therefore, we investigated the effect of the acute sleep restriction on autonomic function and its relation with pain thresholds in healthy subjects. Objectives: Evaluating the relationship between autonomic responses and perception of thermal and electrical nociceptive stimuli after acute sleep restriction caused by stressful work. Methods: We evaluated 19 healthy medical students after normal night of sleep (NS) and after 12-hour night shift (SR). First we examined clinical characteristics of the subjects using scales for assessment of sleep and psychiatric symptoms. Also, we performed quantitative tests of sensitivity to thermal and electrical sensations and recorded double-electric-induced sudomotor skin responses (SSR) at different inter-stimulus intervals (ISI). Results: The total mean duration of sleep was 120 ± 28 minutes out of 12 hours of night shift. The anxiety scores were higher in SR Phase in comparison with those from NS Phase (p<0.01). After SR, there was a decrease in heat pain, but not in warm neither electrical threshold. Regarding autonomic responses, SR subjects showed higher SSR amplitudes and increased number of double responses at ISI 2s. It was also observed a moderate inverse correlation between heat pain thresholds and SSR amplitude (r = -0.45; P<0.01). However, there was no correlation between anxiety scores and SSR parameters. Indeed, in the multivariate linear regression model, heat pain perception was significantly correlated with SSR amplitudes (β = - 0.55; 95% CI, -0.65 to -0.07), but not with anxiety scores (p>0.05). Conclusions: The effects of SR on pain are specific and seem to be not related to general changes in sensory perception. Hyperalgesia was associated with abnormal autonomic responses, but not with increased anxiety, suggesting an association between the nociceptive and autonomic systems, independent of the emotional state.