Biology and therapy of fibromyalgia. New therapies in fibromyalgia

Fibromyalgia is a chronic, musculoskeletal pain condition that predominately affects women. Although fibromyalgia is common and associated with substantial morbidity and disability, there are no US Food and Drug Administration-approved treatments. However, progress has been made in identifying pharmacological and non-pharmacological treatments for fibromyalgia. Recent pharmacological treatment studies have focused on selective serotonin and norepinephrine reuptake inhibitors, which enhance serotonin and norepinephrine neurotransmission in the descending pain pathways and lack many of the adverse side effects associated with tricyclic medications. Promising results have also been reported for medications that bind to the α₂δ subunit of voltage-gated calcium channels, resulting in decreased calcium influx at nerve terminals and subsequent reduction in the release of several neurotransmitters thought to play a role in pain processing. There is also evidence to support exercise, cognitive behavioral therapy, education, and social support in the management of fibromyalgia. It is likely that many patients would benefit from combinations of pharmacological and non-pharmacological treatments, but more study is needed.     

Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome

Genetic and environmental factors may play a role in the etiopathology of fibromyalgia syndrome (FMS) and other related syndromes. There is a high aggregation of FMS in families of FMS patients. The mode of inheritance is unknown but it is most probably polygenic. There is evidence that polymorphisms of genes in the serotoninergic, dopaminergic and catecholaminergic systems play a role in the etiology of FMS. These polymorphisms are not specific for FMS and are associated with other functional somatic disorders and depression. Future genetic studies in the field of FMS and related conditions should be conducted in larger cohorts of patients and ethnically matched control groups.     

Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical practice.     

Biology and therapy of fibromyalgia. Functional magnetic resonance imaging findings in fibromyalgia

Techniques in neuroimaging such as functional magnetic resonance imaging (fMRI) have helped to provide insights into the role of supraspinal mechanisms in pain perception. This review focuses on studies that have applied fMRI in an attempt to gain a better understanding of the mechanisms involved in the processing of pain associated with fibromyalgia. This article provides an overview of the nociceptive system as it functions normally, reviews functional brain imaging methods, and integrates the existing literature utilizing fMRI to study central pain mechanisms in fibromyalgia.     

Biology and therapy of fibromyalgia: pain in fibromyalgia syndrome

Fibromyalgia (FM) pain is frequent in the general population but its pathogenesis is only poorly understood. Many recent studies have emphasized the role of central nervous system pain processing abnormalities in FM, including central sensitization and inadequate pain inhibition. However, increasing evidence points towards peripheral tissues as relevant contributors of painful impulse input that might either initiate or maintain central sensitization, or both. It is well known that persistent or intense nociception can lead to neuroplastic changes in the spinal cord and brain, resulting in central sensitization and pain. This mechanism represents a hallmark of FM and many other chronic pain syndromes, including irritable bowel syndrome, temporomandibular disorder, migraine, and low back pain. Importantly, after central sensitization has been established only minimal nociceptive input is required for the maintenance of the chronic pain state. Additional factors, including pain related negative affect and poor sleep have been shown to significantly contribute to clinical FM pain. Better understanding of these mechanisms and their relationship to central sensitization and clinical pain will provide new approaches for the prevention and treatment of FM and other chronic pain syndromes.     

Beyond cognitive-behavioral therapy for fibromyalgia: addressing stress by emotional exposure,processing, and resolution

I comment on the well-designed trial by Alda and colleagues reported in a recent issue of Arthritis Research and Therapy which demonstrated some benefits of cognitive-behavioral therapy (CBT) for fibromyalgia (FM). CBT in this and other studies provides statistically significant but rather modest benefits for FM. This may be because CBT does not directly address the high rates of victimization, post-traumatic stress disorder, and emotional avoidance experienced by a substantial number of patients with FM. Interventions that encourage emotional exposure, processing, and resolution of stressful or traumatic experiences and relationships hold potential for larger effects for many patients and need to be tested.     

Stress and psychophysiological dysregulation in patients with fibromyalgia syndrome

Fibromyalgia syndrome (FMS) is a prevalent musculoskeletal pain disorder characterized by diffuse pain and associated psychophysiological symptoms. Despite extensive research in the past 3 decades, the etiology and pathophysiology of FMS and effective treatment approaches are yet to be delineated. Recently, it has been suggested that FMS may be related to hypofunctional stress systems, particularly in the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Studies have demonstrated that patients with FMS exhibit lowered sympathoadrenal reactivity to stress. These findings seem to be consistent with the large volume of research indicating the inverse relationship between pain sensitivity and sympathetic reactivity. In this paper, we discuss the role of stress in the pain experience in general, stress in patients with FMS, and review the studies evaluating the ANS and HPA functions in response to various stressors.     

Stress, cognition and the nervous system

Stress, as defined by Selye, is the non-specific response of an organism to any demand made upon it. The response varies in intensity, depending on age, experience and genetic makeup. These demands, or stressors, can be physical, social or psychological. This concept has been challenged by others and the importance of perception and cognition in the stress response is argued strongly here. The role or cognition in reacting to external stressors is reviewed in the light of the three brain model and the differing functions of the right and left hemisphere. Techniques such as drugs and cognitive restructuring for altering perception and cognition are discussed. Cognitive restructuring is an important technique used in psychotherapy to enable patients to achieve more appropriate emotional responses and consequent behaviours.     

集胞藻PCC6803中S2P同源蛋白基因sll0862缺失突变株对热胁迫与氧化胁迫的响应

原核生物中S2P参与应答外界环境刺激,然而行光合作用的蓝细菌-集胞藻PCC6803的S2P同源蛋白功能未知。【目的】考察集胞藻PCC6803中S2P同源蛋白sll0862是否参与外界环境刺激的应答。【方法】监测在高温和氧化胁迫的条件下sll0862基因缺失突变株与野生株在生长速率或存活率上的差异,利用水样调制叶绿素荧光仪(water-PAM,脉冲-振幅-调制叶绿素荧光仪)测量在高温和氧化胁迫的条件下突变株与野生株叶绿素荧光参数的差异,来考察其光合作用差异。【结果】sll0862突变株与野生株在正常的培养环境中生长速率并无差异,但是将sll0862突变株与野生株在48℃加热处理半小时后,sll0862突变株的存活率明显低于野生株。当初始OD730值为0.1的藻液中添加终浓度为1 mmol/L双氧水的时候,sll0862突变株的生长速率比野生株明显低,而且氧化胁迫条件下突变株与野生株的调制叶绿素荧光有差异。【结论】集胞藻PCC6803中sll0862基因的缺失导致突变体对高温与氧化胁迫响应出现缺陷,提示有功能的sll0862参与响应热和氧化胁迫。研究结果为进一步阐述S2P同源蛋白sll0862在集胞藻PCC6803中的功能奠定基础。     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

Heterogeneity of psychophysiological stress responses in fibromyalgia syndrome patients

Dysregulated psychophysiological responses have been observed in patients with fibromyalgia syndrome (FMS), although the results are inconsistent. Surface electromyographic (EMG), systolic and diastolic blood pressure, heart rate (HR), and skin conductance levels (SCLs) were continuously recorded at baseline, and during a series of stress and relaxation tasks in 90 FMS patients and 30 age and sex matched healthy controls (HCs). The patient sample demonstrated lower baseline EMG levels compared to the HCs on all tasks. In contrast, the patients displayed elevated HR and SCL (sympathetic vasomotor and sudomotor indices, respectively) during both stress tasks. A cluster analysis identified four psychophysiological response patterns: 63.3% of HCs showed increased muscle tension and stable cardiovascular responses; 34.8% of FMS patients showed a pattern of increased sympathetic vasomotor reactivity with stable sudomotor and reduced muscular response; 12.2% of FMS patients showed a pattern of increased sympathetic sudomotor reactivity connected with increased sympathetic vasomotor response and reduced muscular response; and, in contrast, 46.7% of FMS patients showed a pattern of parasympathetic vasomotor reactivity and reduced sudomotor as well as muscular response. The identification of low baseline muscle tension in FMS is discrepant with other chronic pain syndromes and suggests that unique psychophysiological features may be associated with FMS. The different psychophysiological response patterns within the patient sample support the heterogeneity of FMS.     

Plasma-binding globulins and acute stress response.

Within studies of acute stress physiology an increase in glucocorticoid secretion is thought to be the primary mediator of tissue response to stress. Corticosteroid-binding globulin may regulate tissue availability of steroids, but has not been considered a dynamic component of the acute stress response. Here, we examined CBG level over the common 60-minute time frame in an acute capture and handling protocol to investigate whether CBG capacity is dynamic or static over short stressors. Using a comparative approach, we measured CBG response to capture and handling stress in nine species of birds, representing five orders and nine families. CBG capacity significantly declined within 30 - 60 minutes of capture in five of the nine species examined. This decline may serve to significantly increase the level of corticosterone reaching tissues during acute stress.     

Stress response and tolerance of the submerged macrophyte Elodea nuttallii (Planch) St. John to heat stress: a comparative study of shock heat stress and gradual heat stress

Sudden and gradual increases of temperature in aquatic environments play important roles in determining growth and physiological dynamics of aquatic macrophytes. However, a lesser attention has been paid to identify the effects of different temperature regimes on aquatic macrophytes. Therefore, the present study is focused on comparing the effects of shock and gradual heat stresses (SHS and GHS) on growth, photosynthetic attributes, and oxidative damage on Elodea nuttallii as a model plant. Laboratory-oriented two experimental setups were maintained to induce the SHS and GHS. A significant decline in shoot elongation coupled with a decline in endogenous indoleacetic acid (IAA) and an increase in hydrogen peroxide (H₂O₂) was observed in both temperature treatments. These effects were further accompanied by oxidative damage to photosynthetic pigments and cell membrane structures in E. nuttallii. Temperature-mediated oxidative stress was significantly pronounced under SHS, which induced the activation of different defensive mechanisms against reactive oxygen species, including antioxidant enzymes, secondary metabolites, and osmoprotectants. The present study revealed that temperature-induced oxidative damage was more severe when the temperature increased suddenly. Further, heat acclimation was observed when the plant was exposed to 30 °C under GHS, although this treatment induces significant oxidative stress under 35 °C.     

创伤后应激障碍（PTSD）的生物学研究概述

创伤后应激障碍（posttraumatic stress disorder,PTSD）是灾害后精神及行为障碍的一种重要表现形式,具有发病率及患病率高、病程长、疗效差等特点,严重影响了临床救治。对于创伤后应激障碍发病机制及其防治的研究日益受到关注。致力于PTSD研究的研究者,从行为学、神经内分泌等宏观研究,到形态学、细胞分子生物学等功能研究,再到临床实验研究,做了大量的工作,得到了许多具有实际指导意义的结果。本文针对国内外研究者近年来在这方面的研究现状进行综述,从宏观上为PTSD后续的研究提供一些循证的证据。     

创伤后应激障碍（PTSD）的生物学研究概述

创伤后应激障碍(posttraumatic stress disorder,PTSD)是灾害后精神及行为障碍的一种重要表现形式,具有发病率及患病率高、病程长、疗效差等特点,严重影响了临床救治。对于创伤后应激障碍发病机制及其防治的研究日益受到关注。致力于PTSD研究的研究者,从行为学、神经内分泌等宏观研究,到形态学、细胞分子生物学等功能研究,再到临床实验研究,做了大量的工作,得到了许多具有实际指导意义的结果。本文针对国内外研究者近年来在这方面的研究现状进行综述,从宏观上为PTSD后续的研究提供一些循证的证据。