Comparing the association of widespread pain,multi-joint pain and low back pain with measures of pain sensitization and function in people with knee osteoarthritis

Clinical Rheumatology - To compare 1. measures of pain sensitization (PS) in people with widespread pain (WSP), multi-joint pain, low back pain (LBP) and knee osteoarthritis (KOA) only, in people...     

小胶质细胞在偏头痛大鼠中枢敏化过程中的作用

目的观察二甲胺四环素(MC)对偏头痛大鼠痛觉超敏行为、颈髓后角小胶质细胞及神经元激活的影响,探讨小胶质细胞在偏头痛大鼠模型中枢敏化过程中的作用。方法 66只雄性SD大鼠随机分为空白组、假手术组、生理盐水组(NS组)、新型致炎剂(IS)4d组(IS4组)、IS 7d组(IS7组)、IS/MC预防组、IS/NS预防组、NS/NS预防组、IS/MC治疗组、IS/NS治疗组、NS/NS治疗组。每组6只。采用Vonfrey纤维丝测定各组大鼠眶周痛觉阈值,免疫荧光染色测定颈髓后角小胶质细胞及神经元激活情况。结果硬脑膜给予IS第3天眶周痛觉阈值较NS组明显下降(P<0.01)。IS/MC预防组眶周痛觉阈值明显高于IS/NS预防组(P<0.01)。IS4组、IS7组小胶质细胞平均荧光密度值高于假手术组(P<0.01)。IS/MC预防组、IS/MC治疗组小胶质细胞平均荧光密度值分别低于IS/NS预防组、IS/NS治疗组(P<0.01)。IS/MC预防组C-fos平均荧光密度值明显低于IS/NS预防组(P<0.01)。结论在慢性硬脑膜炎症所致的中枢敏化过程中小胶质细胞可能仅在启动阶段起作用,对于痛觉超敏的维持无作用。MC能有效预防偏头痛大鼠模型痛觉超敏的发生,但对已存在的痛觉超敏无治疗作用。     

Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome

In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS) experience chronic widespread pain. These pain complaints show the greatest overlap between CFS and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed similarities in both diseases. The knowledge concerning the physiological mechanism of central sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients, on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images. To examine the present hypothesis more research is required. Further investigations could use similar protocols to those already used in studies on pain in FM like, for example, studies on temporal summation, spatial summation, the role of psychosocial aspects in chronic pain, etc. Mira Meeus is financially supported by a Ph.D. grant (“Chronic pain in chronic fatigue syndrome: a biopsychosocial approach”) supplied by the Higher Institute of Physiotherapy, Department of Health Sciences, Hogeschool Antwerpen, Antwerp, Belgium and co-financed by Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel (VUB), Brussels, Belgium (OZR project OZ.R. 1234/MFYS Wer2).     

Treating beyond symptoms with a view to improving patient outcomes in inflammatory bowel diseases

Background and aimsTreatment goals in inflammatory bowel diseases are evolving beyond the control of symptoms towards the tight control of objectively-measured gastrointestinal inflammation. This review discusses the progress and challenges in adopting a treat-to-target approach in inflammatory bowel diseases.MethodsEvidence from the literature that highlights current thinking in terms of treating-to-target in patients with inflammatory bowel diseases is discussed.ResultsMonitoring for objective evidence of inflammation using endoscopy, cross-sectional imaging or laboratory biomarkers may be a useful approach in inflammatory bowel diseases; however, setting the appropriate treatment goal remains a challenge. Deep remission (a composite of symptom control and mucosal healing) may now be a realistic target in Crohn's disease; however, it remains to be proven that achieving deep remission will modify the long-term disease course. Assessing prognosis at an early stage of the disease course is essential for the development of an appropriate management plan, with the rationale of adapting treatment to disease severity. An algorithm has been proposed for the treatment of early Crohn's disease that involves early treatment with immunosuppressants and tumour necrosis factor antagonists, in the hope of preventing structural bowel damage.ConclusionsTreating beyond symptoms will require a clear management plan influenced by disease severity at presentation, clinical and biological prognostic factors, achievement and maintenance of clinical and biological remission and pharmacoeconomics.     

Conditioned pain modulation as a predictor of central sensitization in primary knee osteoarthritis patients

Aim of the workCentral sensitization (CS) is a nervous system disorder associated with chronic pain. This study aimed to quantify pain and evaluate conditioned pain modulation (CPM) and CS in knee osteoarthritis (KOA) patients with chronic pain.Patients and methodsThe study included 50 patients with primary KOA having chronic pain and 50 matched controls. The following assessment tools were used: visual analog scale (VAS)-pain, Western Ontario and McMaster Universities (WOMAC), pain DETECT questionnaire (PD-Q), and central sensitization inventory (CSI). Also, pressure pain threshold (PPT), electrical sensory threshold (EST), and electrical pain threshold (EPT) were assessed at both knees and remote sites. CPM was assessed using the submaximal effort tourniquet method, and the CPM ratio was measured (pre-to-post PPT).ResultsThe patients' mean age was 49.6 ± 9.7 years, 32 females and 18 males (F:M 1.2:1), and disease duration of 7.4 ± 3.6 years. Patients had a significantly higher CPM ratio (1.1 ± 0.21), PD-Q score (20.1 ± 9.1), CSI score (48.8 ± 21.4) compared to the control (0.9 ± 0.07; 8.3 ± 3.9 and 25.5 ± 9.4 respectively; p < 0.0001) and had a lower EPT and PPT in both knees and remote sites (p < 0.0001). CPM was significantly correlated with VAS-pain, WOMAC, CSI, PD-Q and inversely with EPT and PPT at both knees and remote sites and with EST at the right knee (p < 0.0001 each). CPM, PD-Q, and left knee EPT were significant predictors of CS tested with CSI (p < 0.0001, p < 0.0001, and p = 0.004, respectively).ConclusionThere is evidence of CS in KOA patients having chronic pain, and CPM and PD-Q can predict CS.     

Peripheral and central sensitization in musculoskeletal pain disorders: an experimental approach

This report provides a brief introduction to the manifestations of peripheral and central sensitization involved in musculoskeletal pain disorders. It has become increasingly evident that muscle hyperalgesia, referred pain, referred hyperalgesia, and widespread hyperalgesia play an important role in chronic musculoskeletal pain. A better understanding of the involved basic mechanisms and better methods to assess muscle pain in the clinic may provide new possibilities for designing rational therapies and for targeting the pharmacologic intervention optimally. Peripheral sensitization plays an important role for increased sensitivity of deep tissue. However, central sensitization may be equally important but less addressed. Quantitative sensory testing provides the possibility to evaluate these manifestations in a standardized way in patients with musculoskeletal pain or in healthy volunteers (eg, experimentally induced referred pain can be used to assess the potential involvement of central sensitization in musculoskeletal pain conditions). Central sensitization may play a role in the persistence, amplification, and spread of pain. Interventions should take this aspect into consideration.     

Respiratory muscle evaluation of the patient with neuromuscular disease

This review presents clinically relevant issues regarding the assessment of respiratory muscles in individuals with neuromuscular disorders, and discusses the advantages and disadvantages of methods generally available to the clinician. Vital capacity (VC) and total lung capacity (TLC) are routinely measured in pulmonary function laboratories and are typically reduced in the context of severe respiratory muscle weakness, but the sensitivity and specificity of these measures are limited. Better measures of respiratory muscle weakness are maximal static inspiratory and expiratory pressures (PI max and PE max). PI max is reduced even with mild or moderate degrees of inspiratory muscle weakness, but low values also may be related to submaximal effort. To circumvent this problem, pressures can be measured using simpler maneuvers such as a maximal sniff. Specific tests of diaphragm function such as measurements of maximal transdiaphragmatic pressure are invasive and not routinely available to the clinician. Recently, noninvasive methods that specifically assess diaphragm function, such as diaphragm ultrasound of the zone of apposition and magnetic or electrophrenic nerve stimulation, have shown promise as new techniques for clinical use.     

Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain

OBJECTIVE: To examine the effects of pool-based (PE) and land-based (LE) exercise programs on patients with fibromyalgia. METHODS: The outcomes were assessed by the Fibromyalgia Impact Questionnaire, the Arthritis Self-Efficacy Scale, and tests of physical capacity. RESULTS: Eighteen subjects in the PE group and 16 in the LE group performed a structured exercise program. After 20 weeks, greater improvement in grip strength was seen in the LE group compared with the PE group (P < 0.05). Statistically significant improvements were seen in both groups in cardiovascular capacity, walking time, and daytime fatigue. In the PE group improvements were also found in number of days of feeling good, self-reported physical impairment, pain, anxiety, and depression. The results were mainly unchanged at 6 months followup. CONCLUSION: Physical capacity can be increased by exercise, even when the exercise is performed in a warm-water pool. PE programs may have some additional effects on symptoms.     

Validity of the central sensitization inventory with measures of sensitization in people with knee osteoarthritis

Clinical Rheumatology - Our purpose was to determine the validity of the Central Sensitization Inventory (CSI) with psychophysical tests, psychological and physical factors in patients with Knee...     

Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization and pain disinhibition

Chronic musculoskeletal pain has biological, psychological and social components. This review deals with the biological factors, with emphasis on the fibromyalgia syndrome (FMS). Studies on central sensitization of pain-transmitting neurons, changes in endogenous pain modulation that give rise to pain disinhibition, referred pain, pain-related decrease in muscle strength and endurance, and pain generators in deep tissues are reviewed. In FMS there is strong scientific support for the statement that the biological part of the syndrome is a longstanding or permanent change in the function of the nociceptive nervous system that can be equated with a disease. Further research is necessary in order to determine which methods are best for diagnosis of the pain hypersensitivity in clinical practice. FMS may be the far end of a continuum that starts with chronic localized/regional musculoskeletal pain and ends with widespread chronic disabling pain.     

Neurophysiologic evidence for a central sensitization in patients with fibromyalgia

OBJECTIVE: To determine whether abnormalities of peripheral and central nociceptive sensory input processing exist outside areas of spontaneous pain in patients with fibromyalgia (FM) as compared with controls, by using quantitative sensory testing (QST) and a neurophysiologic paradigm independent from subjective reports. METHODS: A total of 164 outpatients with FM who were attending a self-management program were invited to participate in the study. Data for 85 patients were available and were compared with those for 40 non-FM controls matched for age and sex. QST was performed using thermal, mechanical, and electrical stimuli at locations of nonspontaneous pain. Pain assessment was 2-fold and included use of subjective scales and the spinal nociceptive flexion reflex (NFR), a specific physiologic correlate for the objective evaluation of central nociceptive pathways. Questionnaires regarding quality of life and the impact of FM were available. RESULTS: Participants were mainly middle-aged women, with a mean disease duration of 8 years. Between-group differences were significant for neurophysiologic, clinical, and quality of life measures. In patients with FM, peripheral QST showed significantly altered cold and heat pain thresholds, and tolerance to cold pain was radically reduced. The median NFR threshold in patients with FM (22.7 mA [range 17.5-31.7]) was significantly decreased compared with that in controls (33 mA [range 28.1-41]). A cutoff value of <27.6 mA for NFR provided sensitivity of 73% and specificity of 80% for detecting central allodynia in the setting of FM. CONCLUSION: Our results strongly, although indirectly, point to a state of central hyperexcitability of the nociceptive system in patients with FM. The NFR can be used to assess central allodynia in FM. It may also help discriminate patients who may benefit from use of centrally acting analgesics.     

中枢性卒中后疼痛的诊断评价和治疗

中枢性卒中后疼痛(central poststroke pain,CPSP)是卒中后发生的一种神经性疼痛综合征,以与卒中病损相对应的躯体部位疼痛或感觉异常为特征.CPSP在卒中患者中的发生率为1％～12％.确诊CPSP比较困难,主要是由于临床表现的不确定性、常与多种类型的疼痛同时发生以及缺乏明确的诊断标准.CPSP的治疗亦具有挑战性.文章对CPSP的诊断评价和治疗进行了综述.     

The role of central sensitization in shoulder pain: A systematic literature review

IntroductionHyperexcitability of the central nervous system has been suggested to play an important role in pain experienced by patients with unilateral shoulder pain. A systematic literature review following the PRISMA guidelines was performed to evaluate the existing evidence related to the presence of central sensitization in patients with unilateral shoulder pain of different etiologies including those with chronic subacromial impingement syndrome. Studies addressing neuropathic pain (e.g., post-stroke shoulder pain) were not considered.MethodsElectronic databases PubMed, EBSCO, and Web of Science were searched to identify relevant articles using predefined keywords regarding central sensitization and shoulder pain. Articles were included till September 2013. Full-text clinical reports addressing studies of central sensitization in human adults with unilateral shoulder complaints including those diagnosed with subacromial impingement syndrome were included and screened for methodological quality by two independent reviewers.ResultsA total of 10 articles were retrieved for quality assessment and data extraction. All studies were cross-sectional (case–control) or longitudinal in nature. Different subjective and objective parameters, considered manifestations of central sensitization, were established in subjects with unilateral shoulder pain of different etiologies, including those receiving a diagnosis of subacromial impingement syndrome. Overall results suggest that, although peripheral mechanisms are involved, hypersensitivity of the central nervous system plays a role in a subgroup within the shoulder pain population.ConclusionsAlthough the majority of the literature reviewed provides emerging evidence for the presence of central sensitization in unilateral shoulder pain (including those diagnosed with subacromial impingement syndrome), our understanding of the role central sensitization plays in the shoulder pain population is still in its infancy. Future studies with high methodical quality are therefore required to investigate this further.     

Diagnostic strategies for the evaluation of the patient presenting with chest pain

The approach to the patient with chest pain should be a risk-based, goal-driven, and time-dependent process. The entire protocol must be structured around the needs of the highest-risk patients, which places strict time constraints on the primary risk stratification process. Many highest-risk patients can be identified by clear ECG criteria that are the sole indication for specific treatments. However, most chest pain patients do not demonstrate obvious diagnostic criteria and thus must be allocated into secondary risk stratification pathways aimed at determining the likelihood of ACS.The ECG is the simplest, most inexpensive, and most rapid means for primary risk stratification of chest pain patients. It is limited by its relatively low sensitivity, and thus further testing is necessary when it is nondiagnostic. In other cases, the history and physical examination suggest a high-risk presentation. In many of these patients, further secondary risk stratification is necessary. It can be achieved via detection of myocardial necrosis using biochemical markers and detection of ischemia using MPI (and soon by biochemical markers for ischemia). The goals and strategies for using these modalities differ based on the primary risk assignment. Use of structured risk-based protocols ensures that the evaluation is appropriate for the given level of risk. This also allows for the insertion of new risk evaluation technologies as they become available in a manner that optimizes appropriate use and cost effectiveness.When the approach to the evaluation of patients presenting with chest pain proceeds in a systematic fashion, it is possible to evaluate large numbers of patients safely and cost-effectively, even when employing advanced technology. Although the fundamental goal remains the reduction of cardiovascular mortality through the rapid identification and treatment of high-risk patients, the ability to eliminate the inadvertent discharge of patients having an ACS is equally important. Such programs should be inclusive of all patients presenting with potential ACS, should proceed systematically, should consider both diagnostic and prognostic data for risk stratification, and should manage risk through goal and time strategies appropriate to the level of risk. 83     

Erythrocyte sensitization with monomeric IgM in a patient with hemolytic anemia

An automated antiglobulin test showed that erythrocytes of a patient with an acute episode of Coombs-negative hemolytic anemia were strongly sensitized with nonagglutinating IgM molecules. The bound antibodies, after elution from red blood cell stroma, were found to be monomeric IgM, since they migrated with IgG molecules on an agarose column, although they were proved to be immunoglobulin M, not G, by a sensitive hemagglutination inhibition assay. The hemolysis subsided with steroid therapy, but ANA increased to a titer greater than 1,024 (with peripheral pattern) without other laboratory evidence of systemic lupus erythematosus. In addition, the patient demonstrated photosensitivity and non-scarring alopecia. We consider that this appearance of erythrocyte autoantibodies consisting of monomeric IgM was a symptom of atypical SLE.     

Association between chronic pain with presarcopenia and central sensitization in Japanese community-dwelling older adults: A cross-sectional study

Older people with chronic pain are at higher risk of developing sarcopenia. Central sensitization (CS) has been implicated in chronic pain among community-dwelling older adults. However, a relationship between CS and chronic pain with sarcopenia has not been established. This cross-sectional study aimed to clarify the relationship between chronic pain with sarcopenia or presarcopenia and CS among community-dwelling older adults. We assessed chronic pain and sarcopenia in 104 older adults participating in community health checks. We defined sarcopenia using the Asian Working Group for Sarcopenia (AWGS) consensus recommendations based on the following outcomes: low muscle mass, low muscle strength, and slow gait speed. Pain-related assessments included pain intensity, the Pain Catastrophizing Scale, the CS Inventory-9, the pressure pain threshold, the Tampa Scale of Kinesiophobia-11, and the EuroQol 5-dimension 5-level (EQ5D-5L). Chronic pain was defined by related symptoms within the month prior to the health check that had continued for ≥ 3 months and corresponded to a numerical rating scale score of ≥ 1 at the site of maximum pain. The prevalence of chronic pain was 43.3%. In addition, the prevalence of chronic pain with sarcopenia or presarcopenia was 29.8%. A logistic regression analysis revealed that the pressure pain threshold (odds ratio: 0.82, 95% CI: 0.95–1.02) and the EQ5D-5L (odds ratio: 0.58, 95% CI: 0.36–0.76) were significantly associated with the presence of chronic pain with sarcopenia or presarcopenia. Chronic pain with sarcopenia or presarcopenia was affected by central sensitization. Therefore, CS should be evaluated in the elderly.