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

Firm‐specific human capital investments as a signal of general value: Revisiting assumptions about human capital and how it is managed

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136278/1/smj2521.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136278/2/smj2521_am.pd

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

Analysis of a GRACE Global Mascon Solution for Gulf of Alaska Glaciers

We present a high-resolution Gravity Recovery and Climate Experiment (GRACE) mascon solution for Gulf of Alaska (GOA) glaciers and compare this with in situ glaciological, climate and other remote-sensing observations. Our GRACE solution yields a GOA glacier mass balance of -6511 Gt a(exp.-1) for the period December 2003 to December 2010, with summer balances driving the interannual variability. Between October/November 2003 and October 2009 we obtain a mass balance of -6111 Gt a(exp. -1) from GRACE, which compares well with -6512 Gt a(exp. -1) from ICESat based on hypsometric extrapolation of glacier elevation changes. We find that mean summer (June-August) air temperatures derived from both ground and lower-troposphere temperature records were good predictors of GRACE-derived summer mass balances, capturing 59% and 72% of the summer balance variability respectively. Large mass losses during 2009 were likely due to low early melt season surface albedos, measured by the Moderate Resolution Imaging Spectroradiometer (MODIS) and likely associated with the 31 March 2009 eruption of Mount Redoubt, southwestern Alaska. GRACE data compared well with in situ measurements atWolverine Glacier (maritime Alaska), but poorly with those at Gulkana Glacier (interior Alaska). We conclude that, although GOA mass estimates from GRACE are robust over the entire domain, further constraints on subregional and seasonal estimates are necessary to improve fidelity to ground observations

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

Depression and Anxiety in Patients Undergoing Open Heart Surgery: Age and Sexual Differences

Aims: Coronary artery bypass graft surgery is like any other type of surgical procedure for a stressful patient and anxiety and depression are common and important disorders in these patients. The aim of this study is to assess the incidence of anxiety and depression regarding the age and sex differences in patients undergoing open heart surgery. Materials & Methods: In this descriptive cross-sectional study, 205 patients between 30 and 80 years old were selected by available sampling method. Data were collected by a 3section questionnaire, including demographic factor, hospital anxiety and depression scale and State-Trait Anxiety Inventory a day before surgery. The patients were chosen from elective heart surgery in Heshmat hospital of Rasht. The variables were evaluated using chi squre, independent test and one way Anova. Analyses were performed using Spss version 19. Findings: A total of 205 people, 66.3% patients were men and 33% women. 58.1% of men and 55.1% of women were suffering from some degree of depression and this difference was not statistically significant (p=0.8). Considerable different in trait anxiety and state anxiety of The average score of anxiety and depression of the patients was not significantly different in terms of age as well ( Above and under 50). Conclusion: Considering the high incidence of anxiety and depression in these patients, symptoms should be observed and cured , and if necessary preventive psychological and clinical interviews in these patients are recommended

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

Benign perimesencephalic hemorrhage occurring after previous aneurysmal subarachnoid hemorrhage: a case report

<p>Abstract</p> <p>Introduction</p> <p>Both aneurysmal subarachnoid hemorrhage and benign perimesencephalic hemorrhage are well-described causes of spontaneous subarachnoid hemorrhage that arise as a result of different pathologic processes. To the best of the authors' knowledge, there have been no reports of both vascular pathologies occurring in the same individual.</p> <p>Case presentation</p> <p>A 51-year-old Caucasian woman with a history of aneurysmal subarachnoid hemorrhage presented five years after her initial treatment with ictal headache, meningismus, nausea and emesis similar to her previous bleeding event. Computed tomographic imaging revealed perimesencephalic bleeding remote from her previously coiled anterior communicating artery aneurysm. Both immediate and delayed diagnostic angiography revealed no residual filling of the previously coiled aneurysm and no other vascular anomalies, consistent with benign perimesencephalic hemorrhage. The patient had an uneventful hospital course and was discharged to home in good condition.</p> <p>Conclusions</p> <p>This report for the first time identifies benign perimesencephalic hemorrhage occurring in the setting of previous aneurysmal subarachnoid hemorrhage. The presence of a previously treated aneurysm can complicate the process of diagnosing benign perimesencephalic hemorrhage. Fortunately, in this case, the previously treated anterior communicating artery aneurysm was remote from the perimesencephalic hemorrhage and could be ruled out as a source. The patient's prior aneurysmal subarachnoid hemorrhage did not worsen the anticipated good outcome associated with benign perimesencephalic hemorrhage.</p

Impact of human CA8 on thermal antinociception in relation to morphine equivalence in mice

Recently, we showed that murine dorsal root ganglion (DRG) Car8 expression is a cis-regulated eQTL that determines analgesic responses. In this report, we show that transduction through sciatic nerve injection of DRG with human wild-type carbonic anhydrase-8 using adeno-associated virus viral particles (AAV8-V5-CA8WT) produces analgesia in naive male C57BL/6J mice and antihyperalgesia after carrageenan treatment. A peak mean increase of about 4 s in thermal hindpaw withdrawal latency equaled increases in thermal withdrawal latency produced by 10 mg/kg intraperitoneal morphine in these mice. Allometric conversion of this intraperitoneal morphine dose in mice equals an oral morphine dose of about 146 mg in a 60-kg adult. Our work quantifies for the first time analgesia and antihyperalgesia in an inflammatory pain model after DRG transduction by CA8 gene therapy