Towards an optimal therapy strategy for myogenous TMD, physiotherapy compared with occlusal splint therapy in an RCT with therapy-and-patient-specific treatment durations

Appendix. Threshold of signs and symptoms. Post-hoc power analysis on measures of effectiveness. Two-way ANOVA statistical analysis for pain intensity. Rules for progressing and ending splint therapy. Rules for progressing and ending physiotherapy. A stepped-care model including two possible therapies. (PDF 86 kb

Patients' experiences of living with and receiving treatment for fibromyalgia syndrome: a qualitative study

Background: Fibromyalgia syndrome (FMS) presents a challenge for patients and health care staff across many medical specialities. The aetiology is multi-dimensional, involving somatic, psychological and social factors. Patients' views were obtained to understand their experience of living with this long-term condition, using qualitative interviews. Methods: 12 patients were recruited and stratified by age, gender and ethnicity from one rheumatology outpatient clinic, and a departmental held database of patients diagnosed with FMS. Results: Patients' accounts of their experience of FMS resonated well with two central concepts: social identity and illness intrusiveness. These suggested three themes for the analytical framework: life before and after diagnosis (e.g. lack of information about FMS, invisibility of FMS); change in health identity (e.g. mental distress, impact on social life) and perceived quality of care (e.g. lack of contact with nurses, attitudes of specialists). The information provided from one male participant did not differ from the female patients, but black and ethnic community patients expressed a degree of suspicion towards the medication prescribed, and the attitudes displayed by some doctors, a finding that has not been previously reported amongst this patient group. Patients expected more consultation time and effective treatment than they received. Subjective experiences and objective physical and emotional changes were non-overlapping. Patients' accounts revealed that their physical, mental and social health was compromised, at times overwhelming and affected their identity. Conclusion: FMS is a condition that intrudes upon many aspects of patients' lives and is little understood. At the same time, it is a syndrome that evokes uneasiness in health care staff ( as current diagnostic criteria are not well supported by objective markers of physiological or biochemical nature, and indeed because of doubt about the existence of the condition) and places great demands on resources in clinical practice. Greater attention needs to be paid to the links between the explanatory models of patients and staff, and most important, to the interrelationship between the complex physical, psychological and social needs of patients with FMS. Taking a less medical but more holistic approach when drawing up new diagnostic criteria for FMS might match better individuals' somatic and psycho-social symptom profile and may result in more effective treatment

What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

10.1371/journal.pone.0049969PLoS ONE711

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

Fibromyalgia and neuropathic pain - differences and similarities. A comparison of 3057 patients with diabetic painful neuropathy and fibromyalgia

<p>Abstract</p> <p>Background</p> <p>Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities.</p> <p>Methods</p> <p>The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, Pain<it>DETECT</it>). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts.</p> <p>Results</p> <p>Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%).</p> <p>Conclusions</p> <p>DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms - the sensory profile - is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be found in 20-35% of patients of both aetiologies.</p

A computational model for sex-specific genetic architecture of complex traits in humans: Implications for mapping pain sensitivity

Understanding differences in the genetic architecture of complex traits between the two sexes has significant implications for evolutionary studies and clinical diagnosis. However, our knowledge about sex-specific genetic architecture is limited largely because of a lack of analytical models that can detect and quantify the effects of sex on the complexity of quantitative genetic variation. Here, we derived a statistical model for mapping DNA sequence variants that contribute to sex-specific differences in allele frequencies, linkage disequilibria, and additive and dominance genetic effects due to haplotype diversity. This model allows a genome-wide search for functional haplotypes and the estimation and test of haplotype by sex interactions and sex-specific heritability. The model, validated by simulation studies, was used to detect sex-specific functional haplotypes that encode a pain sensitivity trait in humans. The model could have important implications for mapping complex trait genes and studying the detailed genetic architecture of sex-specific differences

Modeling genetic imprinting effects of DNA sequences with multilocus polymorphism data

Single nucleotide polymorphisms (SNPs) represent the most widespread type of DNA sequence variation in the human genome and they have recently emerged as valuable genetic markers for revealing the genetic architecture of complex traits in terms of nucleotide combination and sequence. Here, we extend an algorithmic model for the haplotype analysis of SNPs to estimate the effects of genetic imprinting expressed at the DNA sequence level. The model provides a general procedure for identifying the number and types of optimal DNA sequence variants that are expressed differently due to their parental origin. The model is used to analyze a genetic data set collected from a pain genetics project. We find that DNA haplotype GAC from three SNPs, OPRKG36T (with two alleles G and T), OPRKA843G (with alleles A and G), and OPRKC846T (with alleles C and T), at the kappa-opioid receptor, triggers a significant effect on pain sensitivity, but with expression significantly depending on the parent from which it is inherited (p = 0.008). With a tremendous advance in SNP identification and automated screening, the model founded on haplotype discovery and statistical inference may provide a useful tool for genetic analysis of any quantitative trait with complex inheritance

The Two Sides of Placebo Analgesia: Differential Functional Connectivity Reveals Mechanisms of Placebo Analgesic Response

Nicholas J Bush,1,2 Adriana K Cushnie,2 Jeff Boissoneault,1,2 Sharmagh Aghabeigi,1 Casey Alexander,1 Roland Staud,3 Michael E Robinson1 1Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA; 2Department of Anesthesiology, University of Minnesota - Twin Cities, Minneapolis, MN, USA; 3Department of Medicine, University of Florida, Gainesville, FL, USACorrespondence: Nicholas J Bush, Department of Anesthesiology, University of Minnesota, Minneapolis, MN, 55414, USA, Tel +1 612-624-7357, Email [email protected]: Previous research has demonstrated that placebo induction manipulations can reduce an individual’s pain through non-specific mechanisms, such as expectancy manipulations. However, despite robust research characterizing these effects, individual differences in predicting placebo analgesic responses are not well understood.Methods: Fifty-four healthy pain-free adults over 18 (M=22.8, SD=7.82) were recruited (66.7% women). Participants completed a baseline followed by a placebo session involving the application of an inactive cream in the context of an expectancy-enhancing instruction set while undergoing a functional magnetic resonance imaging scan (fMRI). Painful heat stimuli were applied to the thenar eminence of the right palm. Stimulus intensity was individually calibrated to produce pain ratings of approximately 40 on a 100-point visual analog scale. Generalized psychophysiological interaction (gPPI) was used to assess the group differences in functional connectivity during painful stimulation compared to warmth stimulation.Results: About 68.5% showed a reduction in pain in the placebo condition with an average decrease of 30.3%. Non-responders showed an increase in pain in the placebo condition, with an average increase of 18.6%. Repeated measures ANOVA demonstrated a significant within-subjects interaction between expectancy and responder type (F(1,49)=4.27, p=0.04, ηp2=0.08). Expected pain was significantly associated with pain in the placebo session for the responders (b=0.37, R2=0.29, p< 0.001), but not for the non-responders (b=0.11, R2=0.04, p=0.42). gPPI analysis revealed three clusters exhibiting greater increases in FC in areas related to attention and sensory integration in placebo responders compared to non-responders. One cluster was identified where greater increases in functional connectivity were associated with non-responders compared to responders in regions associated with attention and motor processing.Conclusion: Our results provide evidence that responders and non-responders have differential behavioral and functional responses to acute pain during a placebo analgesic task.Keywords: placebo analgesia, placebo, responder, placebo non-responder, pain, functional connectivit