Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification

AbstractThere is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs.PerspectiveThis brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs

Strategien zur Regulation der Schwarzfäule (Guignardia bidwellii) im ökologischen Weinbau

Die Schwarzfäule tritt in einigen deutschen Weinbaugebieten flächendeckend auf und kann gravierende Ertragsausfälle verursachen. Um die Produktionssicherheit im ökologischen Weinbau zu gewährleisten, wurde ein Kooperationsprojekt mit der Zielsetzung initiiert, Informationen über die Biologie des Schadpilzes zu erarbeiten und Strategien zur Prävention und Bekämpfung der Krankheit unter den spezifischen Bedingungen des ökologischen Weinbaus zu entwickeln. Die Biologie des Schaderregers und seiner Interaktionen mit der Rebe wurde in Hinblick auf die Fruchtkörperentwicklung, die Sporenbildung und den Infektionsprozess eingehend untersucht und in Beziehung zu Witterungsbedingungen und Bewirtschaftungsparametern gesetzt. Die Ergebnisse bilden eine Grundlage für die Einschätzung des Infektionsrisikos und die Entwicklung von Entscheidungshilfen für den Rebschutz. Traditionelle und „pilzwiderstandsfähige“ Rebsorten wurden hinsichtlich ihrer Anfälligkeit für die Schwarzfäule charakterisiert, wodurch den Winzern Informationen für die Auswahl weniger Anfälliger Sorten zum Anbau in Befallsgebieten zur Verfügung stehen. Befallenes Rebholz und befallene Ranken wurden als bedeutende Quellen des Primärinokulums der Schwarzfäule identifiziert. Das Entfernen befallener Blätter bei Laubarbeiten erwies sich als Möglichkeit, das Infektionsrisiko für die Trauben zu reduzieren. Aus einer Vielzahl von Mikroorganismen, Pflanzenextrakten, Pflanzenschutz- und –stärkungsmitteln wurden wirksame Agenzien selektiert und im Freiland unter Praxisbedingungen geprüft. Die Kombination von Pflanzenschutzmitteln auf der Basis von Schwefel und Kupfer war besonders wirksam. Wurde, abhängig vom Entwicklungsstadium und dem Infektionsrisiko, das Kupfer mit Gesteinsmehl ersetzt, ließ sich der Kupferaufwand erheblich reduzieren. Im Gegensatz zu Gewächshausversuchen war die Wirkung saponinhaltiger Pflanzenextrakte im Freiland unzureichend. Bei entsprechender Formulierung zur Verbesserung der Regenfestigkeit könnte das große Potential dieser Pflanzenextrakte jedoch genutzt werden. Aufgrund der Ergebnisse des Forschungsprojekts stehen dem ökologischen Weinbau Informationen als Grundlage eines umfassenden Managementkonzepts für die Schwarzfäule zur Verfügung

Widespread somatosensory sensitivity in naturally occurring canine model of osteoarthritis

Osteoarthritis (OA)-associated pain is a leading cause of disability. Central sensitization (CS), as a result of OA, is recognized as an important facet of human patients' chronic pain and has been measured in people using quantitative sensory testing (QST) testing. The spontaneous canine OA model has been suggested as a good translational model, but CS has not been explored in this model. In this study, QST was performed on dogs with and without spontaneous hip or stifle OA to determine whether OA is associated with CS in this model. Mechanical (von Frey and blunt pressure) and thermal (hot and cold) sensory thresholds obtained in dogs with chronic OA-associated pain (n = 31) were compared with those of normal dogs (n = 23). Dogs were phenotyped and joint-pain scored, and testing was performed at the OA-affected joint, cranial tibial muscle, and dorsal metatarsal region. QST summary data were evaluated using mixed-effect models to understand the influence of OA status and covariates, and dogs with OA and control dogs were compared. The presence of OA was strongly associated with hyperalgesia across all QST modalities at the index joint, cranial tibial muscle, and metatarsal site. Mechanical QST scores were significantly moderately negatively correlated with total joint-pain scores. The spontaneous canine OA model is associated with somatosensory sensitivity, likely indicative of CS. These data further validate the canine spontaneous OA model as an appropriate model of the human OA pain condition

The phenotypic and genetic signatures of common musculoskeletal pain conditions

Musculoskeletal pain conditions, such as fibromyalgia and low back pain, tend to coexist in affected individuals and are characterized by a report of pain greater than expected based on the results of a standard physical evaluation. The pathophysiology of these conditions is largely unknown, we lack biological markers for accurate diagnosis, and conventional therapeutics have limited effectiveness. Growing evidence suggests that chronic pain conditions are associated with both physical and psychological triggers, which initiate pain amplification and psychological distress; thus, susceptibility is dictated by complex interactions between genetic and environmental factors. Herein, we review phenotypic and genetic markers of common musculoskeletal pain conditions, selected based on their association with musculoskeletal pain in previous research. The phenotypic markers of greatest interest include measures of pain amplification and ‘psychological’ measures (such as emotional distress, somatic awareness, psychosocial stress and catastrophizing). Genetic polymorphisms reproducibly linked with musculoskeletal pain are found in genes contributing to serotonergic and adrenergic pathways. Elucidation of the biological mechanisms by which these markers contribute to the perception of pain in these patients will enable the development of novel effective drugs and methodologies that permit better diagnoses and approaches to personalized medicine

NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

Background Red yeast rice (i.e., rice fermented with Monascus spp.), as a food supplement, is claimed to be blood cholesterol-lowering. The red yeast rice constituent monacolin K, also known as lovastatin, is an inhibitor of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase. This article aims to develop a sensitive nuclear magnetic resonance (NMR) method to determine the total statin content of red yeast rice products. Methods The total statin content was determined by a 400 MHz 1H NMR spectroscopic method, based on the integration of the multiplet at δ 5.37-5.32 ppm of a hydrogen at the hexahydronaphthalene moiety in comparison to an external calibration with lovastatin. The activity of HMG-CoA reductase was measured by a commercial spectrophotometric assay kit. Results The NMR detection limit for total statins was 6 mg/L (equivalent to 0.3 mg/capsule, if two capsules are dissolved in 50 mL ethanol). The relative standard deviations were consistently lower than 11%. The total statin concentrations of five red yeast rice supplements were between 1.5 and 25.2 mg per specified daily dose. A dose-dependent inhibition of the HMG-CoA reductase enzyme activity by the red yeast rice products was demonstrated. Conclusion A simple and direct NMR assay was developed to determine the total statin content in red yeast rice. The assay can be applied for the determination of statin content for the regulatory control of red yeast rice products

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions: the OPPERA study

The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). However, anatomical criteria overlook etiology, potentially hampering treatment decisions. This study identified clusters of individuals using a comprehensive array of biopsychosocial measures. Data were collected from a case–control study of 1031 chronic TMD cases and 3247 TMD-free controls. Three subgroups were identified using supervised cluster analysis (referred to as the adaptive, pain-sensitive, and global symptoms clusters). Compared with the adaptive cluster, participants in the pain-sensitive cluster showed heightened sensitivity to experimental pain, and participants in the global symptoms cluster showed both greater pain sensitivity and greater psychological distress. Cluster membership was strongly associated with chronic TMD: 91.5% of TMD cases belonged to the pain-sensitive and global symptoms clusters, whereas 41.2% of controls belonged to the adaptive cluster. Temporomandibular disorder cases in the pain-sensitive and global symptoms clusters also showed greater pain intensity, jaw functional limitation, and more comorbid pain conditions. Similar results were obtained when the same methodology was applied to a smaller case–control study consisting of 199 chronic TMD cases and 201 TMD-free controls. During a median 3-year follow-up period of TMD-free individuals, participants in the global symptoms cluster had greater risk of developing first-onset TMD (hazard ratio = 2.8) compared with participants in the other 2 clusters. Cross-cohort predictive modeling was used to demonstrate the reliability of the clusters

Subjective Sleep Quality Deteriorates Before Development of Painful Temporomandibular Disorder

There is good evidence that poor sleep quality increases risk of painful temporomandibular disorder (TMD). However little is known about the course of sleep quality in the months preceding TMD onset, and whether the relationship is mediated by heightened sensitivity to pain. The Pittsburgh Sleep Quality Index was administered at enrollment into the OPPERA prospective cohort study. Thereafter the Sleep Quality Numeric Rating Scale was administered every three months to 2,453 participants. Sensitivity to experimental pressure pain and pinprick pain stimuli was measured at baseline and repeated during follow-up of incident TMD cases (n=220) and matched TMD-free controls (n=193). Subjective sleep quality deteriorated progressively, but only in those who subsequently developed TMD. A Cox proportional hazards model showed that risk of TMD was greater among participants whose sleep quality worsened during follow-up (adjusted hazard ratio=1.73, 95% confidence limits: 1.29, 2.32). This association was independent of baseline measures of sleep quality, psychological stress, somatic awareness, comorbid conditions, non-pain facial symptoms and demographics. Poor baseline sleep quality was not significantly associated with baseline pain sensitivity or with subsequent change in pain sensitivity. Furthermore the relationship between sleep quality and TMD incidence was not mediated via baseline pain sensitivity nor change in pain sensitivity

Large candidate gene association study reveals genetic risk factors and therapeutic targets for fibromyalgia

Fibromyalgia (FM) represents a complex disorder characterized by widespread pain and tenderness and frequently accompanied by additional somatic and cognitive/affective symptoms. Genetic risk factors are known to contribute to the etiology of the syndrome, but few specific genetic variants have been identified to date and still require replication. In this study, a large scale candidate gene approach was used to examine over 350 genes for association with FM

Efeito do pisoteio animal acumulativo e da fenação nos parâmetros físicos do solo em área com sobressemeadura de misturas forrageiras de estação fria em pastagem de Tifton.

Os sistemas de manejo do solo e de pastagem implicam em mudanças nas propriedades físicas do solo a curto, médio e longo prazo, as quais podem ou não ser restritivas ao desenvolvimento do sistema radicular. Objetivou-se, a avaliação de parâmetros físicos do solo em pastagens de tifton 85 sobressemeado com espécies forrageiras de estação fria, em área pastejada no inverno e na primavera e destinadas a produção de feno no verão. O experimento foi conduzido no Instituto Regional de Desenvolvimento Rural (IRDeR). O experimento foi disposto na forma de blocos ao acaso, com arranjo fatorial triplo (2x3x4) constituído de 2 sistemas de manejo (com e sem pastejo), 3 consórcios (aveia preta + ervilhaca, aveia preta + trevo vesiculoso e aveia preta) e quatro camadas de profundidade, com três repetições. Foram coletadas amostras de solo em quatro camadas de profundidade do solo (0-0,05, 0,05- 0,10, 0,10-0,15, 0,15-0,20 m), em todos os tratamentos, para determinação da umidade gravimétrica, densidade de partícula e densidade do solo. A umidade volumétrica, porosidade total, espaço aéreo e o grau de saturação foram calculados. Não ocorreu diferença na porosidade total nas áreas com e sem pastejo, já para o espaço aéreo, houve diferença entre as mesmas. A área com pastejo apresentou maior espaço aéreo. A densidade de partícula foi menor na camada superficial do solo. A aveia preta proporcionou uma maior umidade gravimétrica na área de exclusão de pastejo. Os valores de densidade do solo e de espaço aéreo não são restritivos ao crescimento radicular em ambas as áreas

Modification of COMT-dependent pain sensitivity by psychological stress and sex

Catecholamine-O-methyltransferase (COMT) is a polymorphic gene whose variants affect enzymatic activity and pain sensitivity via adrenergic pathways. Although COMT represents one of the most studied genes in human pain genetics, findings regarding its association with pain phenotypes are not always replicated. Here, we investigated if interactions among functional COMT haplotypes, stress, and sex can modify the effect of COMT genetic variants on pain sensitivity. We tested these interactions in a cross-sectional study, including 2 cohorts, one of 2972 subjects tested for thermal pain sensitivity (Orofacial Pain: Prospective Evaluation and Risk Assessment) and one of 948 subjects with clinical acute pain after motor vehicle collision (post-motor vehicle collision). In both cohorts, the COMT high-pain sensitivity (HPS) haplotype showed robust interaction with stress and number of copies of the HPS haplotype was positively associated with pain sensitivity in nonstressed individuals, but not in stressed individuals. In the post-motor vehicle collision cohort, there was additional modification by sex: the HPS-stress interaction was apparent in males, but not in females. In summary, our findings indicate that stress and sex should be evaluated in association studies aiming to investigate the effect of COMT genetic variants on pain sensitivity