Photosensitivity Is Associated with Chronic Pain following Traumatic Brain Injury.

Individuals with a history of traumatic brain injury (TBI) report increased rates of chronic pain. Photosensitivity is also a common chronic symptom following TBI and is prevalent among other types of chronic pain. The aim of this study was to better understand the relationship between chronic pain, pain-related disability, and photosensitivity in a TBI population. We quantified participants' visual photosensitivity thresholds (VPT) using an Ocular Photosensitivity Analyzer and measured pressure-pain sensitivity using pressure algometry. Participants also completed a battery of self-report measures related to chronic pain, TBI history, and mental health. A total of 395 participants completed testing, with 233 reporting a history of TBI. The TBI group was divided into 120 symptomatic TBI participants (s-TBI), and 113 asymptomatic TBI participants (a-TBI) based on their Neurobehavioral Symptom Inventory (NSI) scores. Participants in the s-TBI group scored significantly higher on self-reported chronic pain measures compared with a-TBI and no-TBI participants, including the Symptom Impact Questionnaire Revised (SIQR; p < 0.001) and the Michigan Body Map (MBM; p < 0.001). Despite differences in chronic pain complaints, groups displayed similar pressure-pain thresholds (p = 0.270). Additionally, s-TBI participants were more sensitive to light (lower VPT, p < 0.001), and VPT was correlated with SIQR scores across all participants (R = -0.452, p < 0.001). These data demonstrate that photosensitivity is associated with self-reported chronic pain and disability in individuals with chronic TBI symptomatology. Photosensitivity could therefore serve as a simple, more highly quantitative marker of high-impact chronic pain after TBI.

Fibromyalgia: A clinical update.

ABSTRACT: Fibromyalgia (FM) is a chronic pain disorder commonly encountered by advanced practice registered nurses in primary and specialty care. Knowing how to recognize FM and its multiple pain and nonpain symptoms facilitates diagnosis. We propose a four-step approach to diagnosis that can reduce costly referrals and treatment delays, and describe evidence-based interventions.

Chronic Pain Clinical and Prescriptive Practices in the Cannabis Era.

BACKGROUND: To explore how health care providers in the United States are adapting clinical recommendations and prescriptive practices in response to patient use of medical cannabis (MC) for chronic pain symptoms. DESIGN: Literature searches queried MeSH/Subject terms "chronic pain," "clinician," "cannabis," and Boolean text words "practice" and "analgesics" in EBSCOHost, EMBASE, PubMed, and Scopus, published 2010-2021 in the United States. Twenty-one primary, peer-reviewed studies met criteria. METHODS: Studies are synthesized under major headings: recommending MC for chronic pain; MC and prescription opioids; and harm reduction of MC. RESULTS: MC is increasingly utilized by patients for chronic pain symptoms. Clinical recommendations for or against MC are influenced by scopes of practice, state or federal laws, institutional policies, education, potential patient harm (or indirect harm of others), and perceived confidence. Epidemiologic and cohort studies show downward trajectories of opioid prescribing and consumption in states with legal cannabis. However, clinicians' recommendations and prescription practices are nonuniform. Impacts of cannabis laws are clear between nongovernmental and governmental institutions. Strategies addressing MC and opioid use include frequent visits, and, to reduce harm, suggesting alternative therapies and treating substance use disorders. CONCLUSIONS: MC use for chronic pain is increasing with cannabis legalization. Provider practices are heterogenous, demonstrating a balance of treating chronic pain using available evidence, while being aware of potential harms associated with MC and opioids.

Which symptoms best distinguish fibromyalgia patients from those with other chronic pain disorders?

RATIONALE, AIMS AND OBJECTIVES: The primary purpose of this study was to test both classic and novel FM pain and non-pain symptoms to determine their practical efficacy in aiding clinicians to distinguish FM pain from other chronic pain disorders. METHODS: 158 pain patients from two primary care clinics were evaluated with history, physical exam, chart review, and a questionnaire containing 26 exploratory symptoms (10 from the Symptom Impact Questionnaire (SIQR) and 16 from the FM literature)). The symptoms were rated on a 0-10 VAS for severity by those patients reporting pain over the past week. Somers' D and mean severity differences between FM and chronic pain patients without FM were used to rank the discriminatory and diagnostic contributions of symptoms. RESULTS: Fifty patients (14.2%) carried a chart diagnosis of FM, 108 (30.7%) had pain but not FM, and 192 (54.5%) who had neither pain nor FM. Comparing means between the two pain groups, the 5 best differentiating symptoms (all, P < .0001) were: a persistent deep aching over most of my body, poor balance (7.4 vs 3.1), environmental sensitivity (6.8 vs 3.0), tenderness to touch (6.8 vs 3.6) and pain after exercise (8.1 vs 4.1). Notably, VAS pain though significantly higher for FM was least discriminatory (6.5 vs 5.1, P < .001). The five best symptoms generated a ROC = 0.85 and Somers' D = 0.69, an accuracy of 81%, and an odd's ratio of 14.4. CONCLUSIONS: Our results herein suggest that clinicians may be well-served to consider symptoms in addition to those contained in current diagnostic criteria when recognizing FM in their chronic pain patients.

Modeling transport, fate, and removal kinetics of nitrate and orthophosphate using recycled adsorbents for high and low-flow stormwater runoff treatment.

Excessive nitrate and orthophosphate carried by the stormwater runoff potentially lead to eutrophication in surface water bodies. Various green infrastructures are used that commonly consider the biological treatment of nutrients from the runoff. Due to the leaching and clogging complexities in biological mechanisms, the selection of high-flow, eco-friendly, and recycled adsorbents has been advocated to promote the physiochemical treatment of nutrients as an alternative. In this study, column experiments were conducted to investigate the transport, fate, adsorption equilibria, and reaction kinetics of nitrate (NO3-N) and orthophosphate (PO4-P) onto three recycled adsorbents - recycled concrete aggregate (RCA), recycled crushed glass (RCG), rice husks (RH), and a layered media (LM), under high and low-flow conditions. The non-reactive solute transport in columns was investigated through the bromide tracer test. The HYDRUS-1D model was used to estimate adsorption coefficients and reaction kinetics of pollutants in unsaturated media columns. Our results indicated the maximum superficial pore velocity (v = 4.40 cm/s) and dispersion (α = 2.50 cm) in RCA at the low-flow condition. Overall, NO3-N removal at the exhaustion was low in all columns, ranging between 1 and 25%. Conversely, orthophosphate removal was significant (p < 0.05) in RCA (≤94%) under low flow conditions with increased reaction kinetics (kr,d = 3.45 min-1, kr,s = 0.55 min-1) and enhanced adsorption capacity at saturation (qmax = 1.87E+05-2.33E+05 mg/kg). In conclusion, the dissolved-phase reaction kinetics (kr,d) played a significant role apart from the physisorption for the satisfactory removal of orthophosphate in RCA.

Nutrients and solids removal in bioretention columns using recycled materials under intermittent and frequent flow operations.

This research investigated the fate and removal of nitrite (NO2-N), nitrate (NO3-N), orthophosphate (PO4-P), and total suspended solids (TSS) in two bioretention columns, which were designed with three recycled materials. The first column was packed with Recycled Concrete Aggregate (RCA). The second column was a Layered Media (LM), which has layers of RCA with crushed glass and rice husks. The columns were tested under intermittent and frequent operations of synthetic runoff with low and high feed concentrations. The effect of inflow concentration, antecedent dry days (ADD), column age, and the anticipated number of events (EN) was also statistically analyzed on the performance of columns. Depending on column types, nutrient removal was significantly (p < 0.05) increased under frequent flow operations by 26-53% over intermittent. However, TSS removal was notably (p < 0.05) increased by 23-35% under intermittent operations over frequent. Overall, LM showed an increased NO2-N (92 ± 2%) and NO3-N (88% ± 2%) removal under low feed frequent operations and TSS removal (97% ± 2%) under initial intermittent operations. On the contrary, RCA showed a maximum of 99% PO4-P removal under high feed frequent operations. Results showed that the nutrient outflow concentration was found to have a negative correlation with EN and column age and a positive correlation with ADDs throughout the experiments.

Kinetics and thermodynamics of thermal inactivation for recombinant Escherichia coli cellulases, cel12B, cel8C, and polygalacturonase, peh28; biocatalysts for biofuel precursor production.

Lignocellulosic biomass conversion using cellulases/polygalacturonases is a process that can be progressively influenced by several determinants involved in cellulose microfibril degradation. This article focuses on the kinetics and thermodynamics of thermal inactivation of recombinant Escherichia coli cellulases, cel12B, cel8C and a polygalacturonase, peh 28, derived from Pectobacterium carotovorum sub sp. carotovorum. Several consensus motifs conferring the enzymes' thermal stability in both cel12B and peh28 model structures have been detailed earlier, which were confirmed for the three enzymes through the current study of their thermal inactivation profiles over the 20-80°C range using the respective activities on carboxymethylcellulose and polygalacturonic acid. Kinetic constants and half-lives of thermal inactivation, inactivation energy, plus inactivation entropies, enthalpies and Gibbs free energies, revealed high stability, less conformational change and protein unfolding for cel12B and peh28 due to thermal denaturation compared to cel8C. The apparent thermal stability of peh28 and cel12B, along with their hydrolytic efficiency on a lignocellulosic biomass conversion as reported previously, makes these enzymes candidates for various industrial applications. Analysis of the Gibbs free energy values suggests that the thermal stabilities of cel12B and peh28 are entropy-controlled over the tested temperature range.

Effect of surfactants at natural and acidic pH on microbial activity and biodegradation of mixture of benzene and o-xylene.

The aim of this work was to explore the effect of lowering pH and application of surfactants (Brij 35, Tween 20 and Saponin) in increasing bioavailability and biodegradability of benzene and o-xylene (BX) as two hydrophobic VOCs in a liquid mixture. All experiments were conducted at neutral and acidic pH to evaluate the effect of population change from bacteria to fungi on the BX biodegradation. The experiments demonstrated that acclimating wastewater inoculum at pH 4 increased the fungal to bacterial ratio. An increase of 11% for benzene and 22% for o-xylene was observed at pH 4 unamended-culture as compared to pH 7. Brij 35 was chosen as the optimum surfactant which was favorable for enhancing the bioavailability of BX at pH 4. Fitting the experimental data to pseudo first-order biodegradation kinetics model showed the BX were biodegraded faster in the presence of optimum surfactant at pH 7 than pH 4.

Subgrouping a Large U.S. Sample of Patients with Fibromyalgia Using the Fibromyalgia Impact Questionnaire-Revised.

Fibromyalgia (FM) is a heterogeneous and complex syndrome; different studies have tried to describe subgroups of FM patients, and a 4-cluster classification based on the Fibromyalgia Impact Questionnaire-Revised (FIQR) has been recently validated. This study aims to cross-validate this classification in a large US sample of FM patients. A pooled sample of 6280 patients was used. First, we computed a hierarchical cluster analysis (HCA) using FIQR scores at item level. Then, a latent profile analysis (LPA) served to confirm the accuracy of the taxonomy. Additionally, a cluster calculator was developed to estimate the predicted subgroup using an ordinal regression analysis. Self-reported clinical measures were used to examine the external validity of the subgroups in part of the sample. The HCA yielded a 4-subgroup distribution, which was confirmed by the LPA. Each cluster represented a different level of severity: "Mild-moderate", "moderate", "moderate-severe", and "severe". Significant differences between clusters were observed in most of the clinical measures (e.g., fatigue, sleep problems, anxiety). Interestingly, lower levels of education were associated with higher FM severity. This study corroborates a 4-cluster distribution based on FIQR scores to classify US adults with FM. The classification may have relevant clinical implications for diagnosis and treatment response.

Reframing chronic pain as a disease, not a symptom: rationale and implications for pain management.

Chronic pain is a common public health problem that has a detrimental impact on patient health, quality of life (QoL), and function, and poses a substantial socioeconomic burden. Evidence supports the redefinition of chronic pain as a distinct disease entity, not simply a symptom of injury or illness. Chronic pain conditions are characterized by three types of pain pathophysiology (i.e. nociceptive, neuropathic, and centralized pain/central sensitization) influenced by a cluster of coexisting psychosocial factors. Negative risk/vulnerability factors (e.g. mood or sleep disturbances) and positive resilience/protective factors (e.g. social/interpersonal relationships and active coping) interact with pain neurobiology to determine patients' unique pain experience. Viewing chronic pain through a biopsychosocial lens, instead of a purely biomedical one, clinicians need to adopt a practical integrated management approach. Thorough assessment focuses on the whole patient (not just the pain), including comorbidities, cognitive/emotional/behavioral characteristics, social environment, and QoL/functional impairment. As for other complex chronic illnesses, the treatment plan for chronic pain can be developed based on pain subtype and psychosocial profile, incorporating pharmacotherapy and self-management modalities. Preferred pharmacologic treatment of conditions primarily associated with nociception (e.g. osteoarthritis) includes acetaminophen and non-steroidal anti-inflammatory drugs, whereas preferred pharmacologic treatment of conditions primarily associated with neuropathy or central sensitization (e.g. fibromyalgia) includes tricyclic compounds, serotonin-norepinephrine reuptake inhibitors, and α2δ ligands. Education, exercise, cognitive behavioral therapy, and many other non-pharmacological approaches, alone or combined with pharmacotherapy, have been shown to be effective for any type of pain, although they remain underutilized due to lack of awareness of their benefits and reimbursement obstacles.

Selecting US research-intensive doctoral programs in nursing: Pragmatic questions for potential applicants.

Nurses hoping to enter a research intensive doctoral program have a choice of program delivery modes, faculty expertise, and multiple points of entry in addition to the traditional post masters. The American Association of Colleges of Nursing (AACN) lists doctoral programs in nursing in over 300 universities in the United States (U.S.) and Puerto Rico, with most institutions offering more than one type of doctorate. For prospective students who want to maximize their likelihood of significant, sustained scientific impact, identifying research-intensive Doctor of Philosophy (PhD) programs with faculty who have a topic match is key. Embarking on a scientific career requires assessing the curricula and faculty at several institutions. The purpose of this paper is to give prospective students pragmatic guidance in selecting a U.S. research-intensive doctoral program in nursing. We provide a list of published quality indicators in PhD programs as well as potential questions to be addressed to key persons in schools.

Does familiarity with CDC guidelines, continuing education, and provider characteristics influence adherence to chronic pain management practices and opioid prescribing?

OBJECTIVES: (1) To assess providers' experience and knowledge of chronic noncancer pain (CNCP) management. (2) To assess providers' utilization of the Centers for Disease Control and Prevention (CDC) 2016 Guideline for Prescribing Opioids for Chronic Pain. (3) To assess the influence of the 2016 CDC guideline on provider confidence in managing CNCP and adherence to the CDC recommendations. METHODS: A cross-sectional, web-based survey conducted with 417 Oregon prescribing providers, divided into three continuing medical education (CME) groups composed of minimal (0-3), moderate (4-10), and high (≥11) hours of training. RESULTS: The three CME groups were associated with increased use of CDC opioid recommended practices (29.4, 34.2, 38.8; p = 0.001; scale 0-50), opioid conversion confidence (5.5, 6.5, 7.4; p < 0.001; scale 0-9), and confidence in pain management (5.5, 5.9, 6.9; p < 0.001, scale 0-9). Slightly more providers utilized CDC recommended practices than did not (57 vs 43 percent). However, CME groups differed substantially in utilization of CDC practices (42 vs 57 vs 72 percent; p < 0.001). Neither providers' profession (physician vs nurse practitioner [NP]) nor geographic setting (urban vs rural) showed differences in use of recommended practices or general confident in pain management (all p > 0.05); however, physicians were slightly more confident in opioid dose conversion than NPs (6.9 vs 5.9; p < 0. 001, scale 0-9). CONCLUSIONS: Higher hours of recent CME positively benefit provider confidence in pain management and utilization of CDC recommended practices. NPs and rural providers were equivalent to their physician and urban counterparts on confidence and adherence to CDC practices, with minor exceptions.

The role of spousal relationships in fibromyalgia patients' quality of life.

Fibromyalgia (FM) is a chronic pain syndrome that includes debilitating symptoms such as widespread pain and tenderness, fatigue, and poor physical functioning. Research has shown FM patients' choice of coping style and relationship quality with their spouse can impact their mental quality of life (QoL), but no known study has examined the protective nature of relationship quality and coping behaviors on both patient physical and mental QoL in the context of chronic pain. We examined 204 patients with FM on the (a) roles of coping styles and relationship quality on patient quality of life, and (b) moderating effect of relationship quality on the association between negative coping style and patient QoL. A series of multiple regressions found patients' coping styles were not significantly associated with physical QoL, but were significantly associated with mental QoL. Patients' relationship quality with their spouse was significantly associated with mental QoL, but not physical QoL and no significant interactions with negative coping style were found. Our results emphasize the importance of coping styles and relationship quality between patients and their spouses in the context of chronic pain. Clinicians can incorporate the patient's relationship as part of a more holistic approach to care and improving outcomes.

A simple screening test to recognize fibromyalgia in primary care patients with chronic pain.

RATIONALE, AIMS, AND OBJECTIVES: Primary care providers are increasingly expected to recognize and treat fibromyalgia (FM) without significant interaction with rheumatologists. The purpose of this study was to evaluate the potential usefulness of 3 simple measures (tenderness to digital pressure, BP cuff-evoked pain, and a single patient question) as a screening test for possible FM in a patient with chronic pain. METHODS: A total of 352 patients (mean age 50 ± 16.3 years, 70% female) scheduled for routine examination in 2 primary care practices were studied. They were comprised of 52 patients (14.8%) who carried a chart diagnosis of FM, 108 (30.7%) with chronic pain but not FM, and 192 who had neither pain nor FM (54.5%). Subjects were assessed for tenderness to digital pressure at 10 locations, BP cuff-evoked pain, and a single question, "I have a persistent deep aching over most of my body" (0-10). RESULTS: FM patients endorsed the single deep ache question substantially more than those with chronic pain but without FM (7.4 ± 2.9 vs 3.2 ± 3.4; P < .0001) and exhibited greater bilateral digital evoked tenderness (6.1 ± 3.1 vs 2.4 ± 2.4, P < 0.0001), and BP-evoked pressure pain (132.6 mmHg ±45.5 vs 169.2 mmHg ±48.0, P < 0.0001). However, on multivariate logistic regressions, the BP cuff-evoked pain became non-significant. On further analyses, a useful screening test was provided by: (1) pain on pinching the Achilles tendon at 4 kg/pressure over 4 seconds, and (2) and positive endorsement of the question "I have a persistent deep aching over most of my body". CONCLUSION: These results suggest that 2 tests, taking less than 1 minute, can indicate a probable diagnosis of FM in a chronic pain patient. In the case of a positive screen, a follow-up examination is required for confirmation or refutation.

Normalizing fibromyalgia as a chronic illness.

Fibromyalgia (FM) is a complex chronic disease that affects 3-10% of the general adult population and is principally characterized by widespread pain, and is often associated with disrupted sleep, fatigue, and comorbidities, among other symptoms. There are many gaps in our knowledge of FM, such that, compared with other chronic illnesses including diabetes, rheumatoid arthritis, and asthma, it is far behind in terms of provider understanding and therapeutic approaches. The experience that healthcare professionals (HCPs) historically gained in developing approaches to manage and treat patients with these chronic illnesses may help show how they can address similar problems in patients with FM. In this review, we examine some of the issues around the management and treatment of FM, and discuss how HCPs can implement appropriate strategies for the benefit of patients with FM. These issues include understanding that FM is a legitimate condition, the benefits of prompt diagnosis, use of non-drug and pharmacotherapies, patient and HCP education, watchful waiting, and assessing patients by FM domain so as not to focus exclusively on one symptom to the detriment of others. Developing successful approaches is of particular importance for HCPs in the primary care setting who are in the ideal position to provide long-term care for patients with FM. In this way, FM may be normalized as a chronic illness to the benefit of both patients and HCPs.

Molecular and biochemical characterization of recombinant cel12B, cel8C, and peh28 overexpressed in Escherichia coli and their potential in biofuel production.

BACKGROUND: The high crystallinity of cellulosic biomass myofibrils as well as the complexity of their intermolecular structure is a significant impediment for biofuel production. Cloning of celB-, celC-encoded cellulases (cel12B and cel8C) and peh-encoded polygalacturonase (peh28) from Pectobacterium carotovorum subsp. carotovorum (Pcc) was carried out in our previous study using Escherichia coli as a host vector. The current study partially characterizes the enzymes' molecular structures as well as their catalytic performance on different substrates which can be used to improve their potential for lignocellulosic biomass conversion. RESULTS: ß-Jelly roll topology, (α/α)6 antiparallel helices and right-handed ß-helices were the folds identified for cel12B, cel8C, and peh28, respectively, in their corresponding protein model structures. Purifications of 17.4-, 6.2-, and 6.0-fold, compared to crude extract, were achieved for cel12B and cel8C, and peh28, respectively, using specific membrane ultrafiltrations and size-exclusion chromatography. Avicel and carboxymethyl cellulose (CMC) were substrates for cel12B, whereas for cel8C catalytic activity was only shown on CMC. The enzymes displayed significant synergy on CMC but not on Avicel when tested for 3 h at 45 °C. No observed ß-glucosidase activities were identified for cel8C and cel12B when tested on p-nitrophenyl-ß-d-glucopyranoside. Activity stimulation of 130% was observed when a recombinant ß-glucosidase from Pcc was added to cel8C and cel12B as tested for 3 h at 45 °C. Optimum temperature and pH of 45 °C and 5.4, respectively, were identified for all three enzymes using various substrates. Catalytic efficiencies (kcat/Km) were calculated for cel12B and cel8C on CMC as 0.141 and 2.45 ml/mg/s respectively, at 45 °C and pH 5.0 and for peh28 on polygalacturonic acid as 4.87 ml/mg/s, at 40 °C and pH 5.0. Glucose and cellobiose were the end-products identified for cel8C, cel12B, and ß-glucosidase acting together on Avicel or CMC, while galacturonic acid and other minor co-products were identified for peh28 action on pectin. CONCLUSIONS: This study provides some insight into which parameters should be optimized when application of cel8C, cel12B, and peh28 to biomass conversion is the goal.

Mindfulness-Based Stress Reduction for Adolescents with Functional Somatic Syndromes: A Pilot Cohort Study.

OBJECTIVE: To assess the feasibility of a mindfulness-based stress reduction (MBSR) program for adolescents with widespread chronic pain and other functional somatic symptoms and to make preliminary assessments of its clinical utility. STUDY DESIGN: Three cohorts of subjects completed an 8-week MBSR program. Child- and parent-completed measures were collected at baseline and 8 and 12 weeks later. Measures included the Functional Disability Inventory (FDI), the Fibromyalgia/Symptom Impact Questionnaire-Revised (FIQR/SIQR), the Pediatric Quality of Life Inventory, the Multidimensional Anxiety Scale (MASC2), and the Perceived Stress Scale. Subjects and parents were interviewed following the program to assess feasibility. RESULTS: Fifteen of 18 subjects (83%) completed the 8-week program. No adverse events occurred. Compared with baseline scores, significant changes were found in mean scores on the FDI (33% improvement, P = .026), FIQR/SIQR (26% improvement, P = .03), and MASC2 (child: 12% improvement, P = .02; parent report: 17% improvement, P = .03) at 8 weeks. MASC2 scores (child and parent) and Perceived Stress Scale scores were significantly improved at 12 weeks. More time spent doing home practice was associated with better outcomes in the FDI and FIQR/SIQR (44% and 26% improvement, respectively). Qualitative interviews indicated that subjects and parents reported social support as a benefit of the MBSR class, as well as a positive impact of MBSR on activities of daily living, and on pain and anxiety. CONCLUSIONS: MBSR is a feasible and acceptable intervention in adolescents with functional somatic syndromes and has preliminary evidence for improving functional disability, symptom impact, and anxiety, with consistency between parent and child measures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02190474.

Mindful Yoga Pilot Study Shows Modulation of Abnormal Pain Processing in Fibromyalgia Patients.

Published findings from a randomized controlled trial have shown that Mindful Yoga training improves symptoms, functional deficits, and coping abilities in individuals with fibromyalgia and that these benefits are replicable and can be maintained 3 months post-treatment. The aim of this study was to collect pilot data in female fibromyalgia patients (n = 7) to determine if initial evidence indicates that Mindful Yoga also modulates the abnormal pain processing that characterizes fibromyalgia. Pre- and post-treatment data were obtained on quantitative sensory tests and measures of symptoms, functional deficits, and coping abilities. Separation test analyses indicated significant improvements in heat pain tolerance, pressure pain threshold, and heat pain after-sensations at post-treatment. Fibromyalgia symptoms and functional deficits also improved significantly, including physical tests of strength and balance, and pain coping strategies. These findings indicate that further investigation is warranted into the effect of Mindful Yoga on neurobiological pain processing.

Genome-wide expression profiling in the peripheral blood of patients with fibromyalgia.

OBJECTIVES: Fibromyalgia (FM) is a common pain disorder characterized by nociceptive dysregulation. The basic biology of FM is poorly understood. Herein we have used agnostic gene expression as a potential probe for informing its underlying biology and the development of a proof-of-concept diagnostic gene expression signature. METHODS: We analyzed RNA expression in 70 FM patients and 70 healthy controls. The isolated RNA was amplified and hybridized to Affymetrix® Human Gene 1.1 ST Peg arrays. The data was analyzed using Partek Genomics Suite version 6.6. RESULTS: Fibromyalgia patients exhibited a differential expression of 421 genes (p<0.001), several relevant to pathways for pain processing, such as glutamine/glutamate signaling and axonal development. There was also an upregulation of several inflammatory pathways and downregulation of pathways related to hypersensitivity and allergy. Using rigorous diagnostic modeling strategies, we show "locked" gene signatures discovered on Training and Test cohorts, that have a mean Area Under the Curve (AUC) of 0.81 on randomized, independent external data cohorts. Lastly, we identified a subset of 10 probesets that provided a diagnostic sensitivity for FM of 95% and a specificity of 96%. We also show that the signatures for FM were very specific to FM rather than common FM comorbidities. CONCLUSIONS: These findings provide new insights relevant to the pathogenesis of FM, and provide several testable hypotheses that warrant further exploration and also establish the foundation for a first blood-based molecular signature in FM that needs to be validated in larger cohorts of patients.