No description available.

Stress can have influence on pain sensitivity, but the direction of its effects remains unclear. Previous research has reported both increased and decreased pain sensitivities under stress with different sensory tasks. The aim of the current study was to investigate the effect of stress on pain sensitivity using multiple psychological stressors in a relatively large sample of young men and women. Sixty-two participants were included, and pain thresholds, tolerance, and temporal summation were tested using thermal, mechanical, and dynamic tasks before and after stress. A condition of stress was induced by the Stroop task and a mental arithmetic task. On average, there were no significant differences between stress and no stress conditions. Although not significant, pressure thresholds and tolerance had a tendency to decrease under stress conditions, and thermal thresholds and tolerance had a tendency to increase under stress conditions. Temporal summation did not change regardless of condition. These findings suggest that individual differences in response to stress and type of task being completed may play a role in how stress affects pain sensitivity. / 2021-06-17T00:00:00Z

In searching for new human pain models that more closely resemble clinical pain states, the capsaicin pain model has emerged as a viable model for both inflammatory and neuropathic pain states. A principal benefit of the capsaicin model is that it allows study of two different pain processes, primary and secondary hyperalgesia. Primary hyperalgesia is characterized by spontaneous pain and both heat and mechanical hyperalgesia. In addition, it is likely the result of activation and sensitization of both peripheral and central nociceptors. In contrast, secondary hyperalgesia is characterized by only mechanical hyperalgesia and is caused by the sensitization of central nociceptive neurons. Previous research utilizing the capsaicin pain model has primarily focused on the neural properties with little focus on the impact of affective states on capsaicin-related pain processes. The present study examined the impact of a noise stressor on both primary and secondary hyperalgesia. Results indicated that the effects of the noise stressor impacted secondary hyperalgesia, but not primary hyperalgesia.

Animal research has elucidated the neurobiological substrates and environmental determinants of pain modulation. Despite these advances, relatively little is known about how psychological processes activate pain modulatory systems. One psychological process that is thought to play an important role in regulating pain sensitivity is emotion. In addition, previous research into the human menstrual cycle and the animal estrous cycle have determined that either the presence of certain gonadal hormones or the fluctuations of these hormones may lead to changes in how females perceive pain, regulate emotion, and modulate pain. The present study examines both the role of emotion and the human menstrual cycle in pain modulation. Participants were 39 female undergraduate students with a mean age of 18.7 years (SD=1.46). Results are consistent with prior studies indicating that progesterone has antiinflammatory effects. Specifically, significant effects were observed primarily in the luteal phase. Subjects in the luteal phase demonstrated less sympathetic arousal during the experiment but greater autonomic arousal during the noise stressor. Participants in the luteal phase also demonstrated an analgesic/anti-inflammatory response evidenced by an observed decrease in secondary hyperalgesia for those that did not receive the noise stressor. No such changes in pain perception were discovered in the ovulation and follicular phases. Finally, in response to the noise stressor, an inhibition of the analgesic/anti-inflammatory effects was observed in the luteal phase. No such evidence of stress-induced pain modulation was discovered in the ovulation and follicular phases. Although the specific mechanisms of this action still remain unclear, prior evidence points to the role of centrally-mediated pain modulation. It is likely that the stressor worked to inhibit the anti-inflammatory effects commonly observed in the luteal phase to persistent inflammatory pain through centrally-mediated pain modulatory mechanisms. It is hypothesized that hormone-mediated effects at the level of the amygdala influenced the impact of affective pain modulation.

In searching for new human pain models that more closely resemble clinical pain states, the capsaicin pain model has emerged as a viable model for both inflammatory and neuropathic pain states. A principal benefit of the capsaicin model is that it allows study of two different pain processes, primary and secondary hyperalgesia. Primary hyperalgesia is characterized by spontaneous pain and both heat and mechanical hyperalgesia. In addition, it is likely the result of activation and sensitization of both peripheral and central nociceptors. In contrast, secondary hyperalgesia is characterized by only mechanical hyperalgesia and is caused by the sensitization of central nociceptive neurons. Previous research utilizing the capsaicin pain model has primarily focused on the neural properties with little focus on the impact of affective states on capsaicin-related pain processes. The present study examined the impact of a noise stressor on both primary and secondary hyperalgesia. Results indicated that the effects of the noise stressor impacted secondary hyperalgesia, but not primary hyperalgesia.

Orientador: Carlos Amilcar Parada / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T21:05:03Z (GMT). No. of bitstreams: 1 Dias_ElayneVieira_D.pdf: 15528641 bytes, checksum: d53f9d8a514c6239af90a41cfe787afb (MD5) Previous issue date: 2013 / Resumo: O resumo poderá ser visualizado no texto completo da tese digital / Abstract: The complete abstract is available with the full electronic document / Doutorado / Fisiologia / Doutora em Biologia Funcional e Molecular

Background: While pain is essential for physiological functioning, chronic or pathologic pain is responsible for a major burden of disease in society. Novel approaches to treating acute and chronic pain have employed neuromodulatory tools to target the central and peripheral neural structures that mediate pain. Transcranial direct current stimulation (tDCS), for example, is a safe, non-invasive brain stimulation technique that has been shown in preliminary studies to reduce chronic pain when applied to the primary motor cortex. In contrast to this exogenous neuromodulatory approach, diffuse noxious inhibitory controls (DNIC) refers to endogenous pain regulatory mechanisms that decrease pain following introduction of heterotopic noxious stimuli. This thesis explores whether combining these exogenous and endogenous pain modulation approaches synergistically increases the threshold at which pain is perceived. Methods: We conducted a double-blinded, randomized, placebo-controlled trial with a crossover design to investigate the effects of tDCS and DNIC on pain thresholds in 15 healthy human subjects. Pain thresholds were assessed prior to and following administration of active tDCS, sham tDCS, cold-water-induced DNIC, and combined active tDCS and DNIC. Using magnetic resonance spectroscopy, we examined whether baseline concentrations of brain metabolites such as N-acetylaspartate in pain-related regions of interest were associated with responses to the varying neuromodulatory conditions. Results: Pain thresholds significantly increased following both active tDCS and the DNIC paradigm. These modulatory approaches appeared to have additive effects when combined. Pain threshold increases after active tDCS were positively correlated with baseline levels of N-acetylaspartate, a marker of good neural function, in the anterior cingulate cortex and negatively correlated with baseline levels of glutamine in the thalamus. Conclusions: Combining endogenous pain regulatory mechanisms with exogenous stimulation of the motor cortex can more effectively increase pain thresholds in healthy humans. Future studies should examine whether existing pain therapies may be enhanced with noninvasive brain stimulation and activation of DNIC. They should also assess whether brain metabolite levels can be utilized to predict clinical response to therapeutic interventions.

A significant driver of pain in low back pain (LBP) is alteration to endogenous pain modulation (EPM). EPM can be measured using quantitative sensory tests (QST), which provides important information on nociceptive pathways. Exercise therapy is recommended as the first line of care for LBP; however, there is limited information on the mechanisms of action that lead to symptom improvements. The first manuscript was a scoping review that summarized protocols used to assess EPM using QST such as pain pressure threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM) or exercise-induced hypoalgesia (EIH) in LBP. Scientific databases were searched for articles that used QST or EIH protocols in LBP. In total, 193 studies were included in this review: 172 used PPT, 54 used TS and 53 used CPM and 5 investigated EIH. There was high variability in the type of equipment, timing, trials, and testing location with many studies not reporting this information. The results demonstrate a need for standardized protocols and reporting guidelines as well as further research to aid in selecting the most appropriate QST parameters for different clinical presentations. The second manuscript was a pilot study that assessed the feasibility of a protocol investigating if changes in EPM occur after exercise therapy. Participants were recruited through a larger trial (WELBack) and were randomized to receive one of two exercise therapies. Participants attended two testing sessions (before and after an 8-week treatment) consisting of PPT, TS, CPM and EIH. Thirty-six participants were recruited and completed baseline assessments. In total, 32 (88.9%) participants completed the follow-up assessment. The results demonstrated that the protocol was feasible. Improvements to patient reported outcomes were seen, but not to all EPM measures. Future work should consider changes to the CPM protocol, and a fully powered study to investigate EPM changes after exercise therapy. / Thesis / Master of Health Sciences (MSc) / Low back pain (LBP) may occur because of changes in our nervous system, rather than a physical injury. However, there is no previous research on if exercise can improve these changes. The purpose of this thesis was to develop and test a protocol to assess how the body processes pain, and if this can change after exercise. We summarized past research on how four tests to assess pain processing have been performed. The results showed many differences in how these tests were performed and reported. More consistency and guidelines are needed to improve how these tests are conducted. Next, we conducted a study aimed to assess the feasibility of a protocol to see if changes occur in how the body processes pain after an exercise therapy program. The results of this study showed the protocol was feasible, and trends in improvement on some but not all measures.

Background: Altered autonomic nervous system (ANS) function has been proposed as a mechanism in the development of central sensitisation (CS) and visceral pain hypersensitivity (VPH). The contribution of the parasympathetic nervous system (PNS) and the factors that mediate differences in sensitisation to acid are unclear and their study will clarify risk factors for oesophageal pain hypersensitivity (OPH) in gastrooesophageal reflux disease. Aims: To investigate psychophysiological and pharmacological manipulation of PNS tone in the development of OPH, and to determine factors which predict the development of OPH to acid infusion in healthy volunteers in a validated model of acid induced OPH. Methods: Pain thresholds to electrical stimulation in the proximal oesophagus were determined before and after a 30-minute distal oesophageal infusion of 0.15 mol/L hydrochloric acid in subjects. Sympathetic (SNS) and PNS parameters were measured at baseline and continuously thereafter. Subjects underwent psychological profiling for anxiety, depression, attachment vulnerability and personality type. Using this model, five studies were undertaken: Study 1 a pilot study to trail modulation suitability for further study used. In Study 2, subjects who demonstrated secondary hyperalgesia in the proximal non-acid-exposed oesophagus performed deep or sham breathing. Study 3 subjects, who did not sensitise to acid, underwent a validated stress test to induce OPH. With Study 4, deep breathing with IV saline (placebo) or atropine (PNS antagonist) was used to evaluate deep breathing’s induced PNS tone in OPH reduction. Study 5, a genetic pilot study, exploring the role of the GCH-1 haplotype in VPH. Results: ANS control’s key role in CS was clarified. Deep breathing increased PNS tone and prevented acid-induced OPH in comparison to sham breathing and confirmed increased PNS tone’s reversal of OPH. Psychological factors of anxiety, alexithymia and attachment status influence ANS modulation of CS. Individuals’ predisposition to VPH due to psychogenetic profiles were clarified and their biopsychosocial role illustrated. Conclusions and Inferences: A mechanistic explanation for the analgesic effect of deep breathing is provided with potential therapeutic implications in the treatment of VPH syndromes. Further clinical study is warranted to develop cost-effective treatments for chronic VPH syndromes.

Introdução: A mensuracão da dor através de testes psicofísicos, entre eles o teste de quantificação sensitiva, definido como a determinação de limiares a estímulos álgicos controlados, possibilita o estudo de inúmeras variáveis que influenciam a percepção final da dor. Entre essas variáveis encontram-se o BDNF (Brain Derived Neurotrophic Factor), o gênero e sistemas modulatórios não classicamente descritos como o melatonérgico. Objetivos: Validar um equipamento para realização do teste de quantificação sensitiva usando amostra de voluntários brasileiros saudáveis e estudar fatores e sistemas neurobiológicos que alteram os limiares nociceptivos como sexo, BDNF e melatonina. Métodos: O novo equipamento (Heat Pain Stimulator-1.1.10; Brazil) foi utilizado em 20 voluntários saudáveis e em pacientes com neuropatia periférica, em duas sessões separadas, para acessar a reprodutibilidade dos limiares e a concordância com os equipamentos clássicos. Em etapa posterior, os limiares de dor foram medidos em voluntários e correlacionados com o gênero e os níveis de BDNF. Em estudo sucessivo 61 sujeitos foram randomizados em 1 dos 4 grupos: placebo, 0,05 mg/kg de melatonina sublingual (SL), 0,15 mg/kg de melatonina SL ou 0,25 mg/kg de melatonina e foram testados quanto aos limiares e tolerância à dor aos estímulos térmico e de pressão no tempo basal e 30 min após a intervenção. A sedação foi quantificada através de escala análogo-visual e pela análise do índice bispectral. Resultados: Os resultados iniciais mostraram concordância com a literatura e adequada reprodutibilidade dos limiares de dor térmica em indivíduos saudáveis (44.5±2.5°C ) e em indivíduos com neuropatias de fibras finas (49.9±3°C) em sessões separadas. Quando analisados em modelo de regressão linear multivariada, os limiares de dor térmica e de pressão mostraram um efeito significativo do gênero (p=0,01 para ambos os modelos), BDNF (p<0,04 para ambos os modelos) e interação entre BDNF e gênero (<0,001 para ambos os modelos). Altos níveis de BDNF foram correlacionados com alto limiar de dor em mulheres e essa relação foi inversa em homens. No estudo com a melatonina, os níveis plasmáticos foram proporcionais à dose administrada, e o modelo de regressão linear mostrou uma relação entre a concentração sérica de melatonina e as modificações nos limiares (R2=0,56 para o limiar de dor ao estímulo térmico e R2=0,518 para o limiar de dor na algometria de pressão). Uma dose única de melatonina igual ou acima de 0,15 mg/kg propiciou um delta médio dos limiares de dor ao estímulo térmico e à pressão maiores que placebo (MANOVA, p<0,05 para todas as análises). Além disso, dose igual ou acima que 0,15 mg/kg produziu maior escore de sedação. Conclusões: O equipamento desenvolvido produz resultados confiáveis para avaliação das vias nociceptivas em voluntários saudáveis e em pacientes com alterações sensitivas. O BDNF está associado a maiores limiares de dor nas mulheres (menos dor), mas tem efeito oposto nos homens, suportando a ideia de que ele modifica o efeito que o gênero exerce sobre os limiares de dor. A melatonina possui efeito analgésico dose-dependente no modelo de dor experimental desenvolvido, havendo correlação entre a concentração plasmática e as alterações nos limiares avaliados. O adequado perfil farmacocinético, e a ausência de efeitos colaterais significativos reforçam a sua consolidação como um fármaco modulador da dor. / Background: The measurement of pain through psychophysical tests, including quantitative sensory testing, allow for the study of many variables that influence the final perception of pain. Among these variables are BDNF (Brain Derived Neurotrophic Factor), in addition to gender and modulatory systems not classically described as melatonergic. Objectives: To validate a device to perform the quantitative sensory testing in a cohort of Brazilian healthy volunteers in order to study factors and neurobiological systems that alter the nociceptive thresholds including gender, BDNF, and melatonin. Methods: The new equipment (Heat Pain Stimulator, 01/01/10, Brazil) was tested on 20 healthy volunteers and patients with peripheral neuropathy in two separate sessions to access the reproducibility of thresholds with the classic features. In later stage, the pain thresholds were measured in volunteers and correlated with gender and levels of BDNF. 61 successive study subjects were randomized into one of four treatment groups: placebo, 0.05 mg / kg of melatonin sublingual (SL), 0.15 mg / kg of melatonin SL or 0.25 mg / kg of melatonin SL, and were tested for thresholds and pain tolerance to thermal and pressure stimuli at baseline and 30 min post intervention. Sedation was quantified by visual analog scale and the bispectral index analysis. Results: Initial results showed agreement with the literature and adequate reproducibility of thermal pain thresholds in healthy subjects (44.5 ± 2.5 ° C) and in patients with neuropathies of fine fibers (49.9 ± 3 ° C) in separate sessions. When analyzed in a multivariate linear regression model, the thermal and pressure pain thresholds showed a significant effect of gender (p = 0.01 for both models), BDNF (p <0.04 for both models) and correlation between BDNF and gender (<0.001 for both models). High levels of BDNF were correlated with high pain threshold in women and this relationship was reversed in men. In the study with melatonin, plasma levels were proportional to dose, and linear regression model showed a relationship between serum melatonin and changes in thresholds (R2 = 0.56 for pain threshold to thermal stimulation and R2 = 0.518 for the threshold of pain on pressure algometry). A single dose of melatonin at or above 0.15 mg / kg led to a delta average pain thresholds to thermal stimulation and a pressure greater than placebo (MANOVA, p <0.05 for all analyzes). Furthermore, a dose equal to or greater than 0.15 mg / kg produced the highest score of sedation. Conclusion: The heat pain stimulator produces reliable results for assessment of nociceptive pathways in healthy volunteers and in patients with sensory changes. BDNF has a facilitatory effect on pain thresholds in women, but has the opposite effect in men, supporting the idea that it modifies the effect gender has on the threshold of pain. Melatonin has a dose-dependent analgesic effect in the experimental pain model developed, there was no correlation between plasma concentration and changes in the thresholds evaluated. The appropriate pharmacokinetic profile, and the absence of significant side effects reinforce its consideration as a pain modulator drug.