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Background and aims Pain is a prevalent problem in many countries. Women are more often on sick-leave for pain than men. Such gender differences have been explained through biological factors, different demands for on the job market, and home conditions. Fewer studies have focused on how gender stereotypes may bias the medical assessment of pain patients. The aim of the present research was to investigate if a gender bias in medical students' evaluations of chronic pain patients can contribute to explaining the gender differences in sick-leave due to pain. Specifically, we investigated whether medical students' estimates of a patient's accuracy of their own work ability and amount of domestic work differed between female and male patients, and how such estimates influenced the medical students' judgments of the patient's work ability. Methods Medical students (n=137; 60 women; 74 men; three unspecified) read a vignette describing a patient with pain and filled out a questionnaire. The vignette was identical and gender neutral, except for the name of the patient signaling gender. A between-subjects experimental design was used in which participants were randomly assigned to an experimental condition. Participants then judged the patient's work ability, the accuracy of the patient's self-assessed work ability, and the amount of domestic work they believed was performed by the patient. All ratings were made on seven-point items. Results The results showed that there was no main effect of gender on perceived future work ability of the patient, F (1,131)=0.867, p=0.353. However, male patients were considered to be more accurate in their self-assessed work ability than female patients F (1,131)=5.925 p=0.016 (Mfemale=4.87, SDfemale=1.22, and Mmale=5.33, SDmale=1.02). Moreover, female patients were thought to perform more domestic work, F (1,131)=25.56, p<0.001 (Mfemale=4.14, SDfemale=1.41, and Mmale=3.07, SDmale=1.16). Finally, perceived amount of domestic work moderated the effects of perceived future work ability for female but not for male patients, B=0.42, p=0.005. Hence, there was a positive effect of amount of domestic work performed on work ability judgments for women, such that the more domestic work they were assumed to perform, the more they were perceived to be able to work. Conclusions Gender stereotypes influenced assessments of future work ability in pain patients, mainly because women were assumed to perform more domestic work which had a positive effect on perceived work ability. Because domestic work should have a negative effect on recovery, expectations from the physician that domestic work is expected by female patients may in fact have the opposite effect prolonging sick-leave. Moreover, the students trusted the male patients' ability to assess their own work capacity more than women's. Implications It is important that medical students receive education about gender biases and how they may influence medical assessment during their training. Such education may alleviate the influence of gender stereotypes.
Learn More >To develop predictive models for short-term and long-term clinically important improvement in women with non-specific chronic disabling neck pain during the clinical course of physiotherapy.
Learn More >Spinal muscular atrophy (SMA) is a devastating motor neuron degeneration disease caused by a deficiency of the SMN protein. Majority of patients also suffer from chronic pain. However, the pathogenesis of pain in the context of SMA has never been explored. In this study, using various pain tests, we found that a mild SMA mouse model presents with multiple forms of pain hypersensitivity. Patch-clamp recording showed that nociceptive neurons in SMA mouse dorsal root ganglia (DRGs) are hyperexcitable and their sodium current densities are markedly increased. Using quantitative RT-PCR, western blotting and immunofluorescence, we observed enhanced expression of two main voltage-gated sodium channels Na1.7 and Na1.8 in SMA mouse DRGs, which is at least in part due to increase in both expression and phosphorylation of NF-κB p50/p65 heterodimer. Moreover, we revealed that plasma norepinephrine levels are elevated in SMA mice, which contributes to mechanical hypersensitivity via the β2-adrenergic receptor. Finally, we uncovered that β2-adrenergic signaling positively modulates expression as well as phosphorylation of p50 and p65 in SMA mouse DRGs. Therefore, our data demonstrate that SMA mice, similar to humans, also develop pain hypersensitivity, and highlight a peripheral signaling cascade that elicits the mechanical sensitization in the mouse model, suggesting potential targets for therapeutic intervention.
Learn More >Reports show that stressful events before injury exacerbates post-injury pain. The mechanism underlying stress-induced heightened thermal pain is unclear. Here, we examined the effects of chronic intermittent stress (CIS) on nociceptive behaviors and brain-derived nerve growth factor (BDNF) system in the prefrontal cortex (PFC) and hypothalamus of rats with and without thermal injury.
Learn More >Background and aims Recent research indicates a previously unknown low-grade systemic or neurogenic inflammation in groups of chronic pain (CP) patients. Low-grade inflammation may have an important role in symptoms that have previously not been well depicted: widespread pain, tiredness and cognitive dysfunctions frequently seen in severely impaired CP patients. This study aimed to investigate the plasma inflammatory profile in a group of very complex CP patients at baseline and at a 1-year follow-up after participation in a cognitive behavior therapy (CBT)-based multimodal pain rehabilitation program (PRP). Methods Blood samples were collected from 52 well-characterized CP patients. Age- and sex-matched healthy blood donors served as controls. The samples were analyzed with a multiple Proximal Extension Analysis allowing a simultaneous analysis of 92 inflammation-related proteins consisting mainly of cytokines, chemokines and growth-factors. At follow-up, 1-year after participation in the RPR samples from 28 patients were analyzed. The results were confirmed by a multi-array technology that allows quantitative estimation. Results Clear signs of increased inflammatory activity were detected in the CP patients. Accepting a false discovery rate (FDR) of 5%, there were significant differences in 43/92 inflammatory biomarkers compared with the controls. In three biomarkers (CXCL5, SIRT2, AXIN1) the expression levels were elevated more than eight times. One year after the PRP, with the patients serving as their own controls, a significant decrease in overall inflammatory activity was found. Conclusions Our results indicate that the most impaired CP patients suffer from low-grade chronic systemic inflammation not described earlier with this level of detail. The results may have implications for a better understanding of the cluster of co-morbid symptoms described as the "sickness-syndrome" and the wide-spread pain seen in this group of patients. The decrease in inflammatory biomarkers noted at the follow-up after participation in the PRP may reflect the positive effects obtained on somatic and psycho-social mechanisms involved in the inflammatory process by a rehabilitation program. Besides the PRP, no major changes in medication or lifestyle factors were implemented during the same period. To our knowledge, this is the first study reporting that a PRP may induce inflammatory-reducing effects. Further studies are needed to verify the objective findings in CP patients and address the question of causality that remains to be solved. Implications The findings offer a new insight into the complicated biological processes underlying CP. It may have implications for the understanding of symptoms collectively described as the "sickness-syndrome" – frequently seen in this group of patients. The lowering of cytokines after the participation in a PRP indicate a new way to evaluate this treatment; by measuring inflammatory biomarkers.
Learn More >Itch consists of both sensory and affective components. For chronic itch patients, the affective component of itch affects both quality of life (leading to psychological comorbidities) and disease prognosis (by promoting scratching of itchy skin). We found that acute itch stimuli such as histamine induced anxiety-like behavior and increased activity (c-Fos expression) in the amygdala in adult male C57BL/6 mice. Itch stimuli also increased activity in projection areas to the amygdala, suggesting that these regions form a circuit for affective itch processing. Electrophysiological characterization of histamine-responsive amygdala neurons showed that this population was active on a behaviorally relevant timescale and partially overlapped with pain signaling. Selective optogenetic activation of histamine-responsive amygdala neurons in adult male and female Fos:CreER;R26 mice using the Targeted Recombination in Active Populations system enhanced both scratching and anxiety-like behavior. These results highlight the importance of itch-responsive amygdala neurons in modulating itch-related affect and behavior.The sensation of itch includes an affective component that leads to stress and anxiety in chronic itch patients. We investigated the neuronal basis of affective itch in mice, with a focus on the amygdala, the key brain region for the generation of anxiety. A subpopulation of amygdala neurons responded to itch stimuli such as histamine. Optogenetic activation of histamine-responsive amygdala neurons affected both scratching and anxiety-like behavior. Therefore, this population appears to be important for mediating the affective component of itch.
Learn More >Background and aims Complex Regional Pain Syndrome (CRPS) often recovers spontaneously within the first year, but when it becomes chronic, available rehabilitative therapies (pharmacological management, physiotherapy, and psychological intervention) have limited effectiveness. This study examined the effect of a 12-week intensive outpatient rehabilitation on pain relief and function in chronic CRPS patients. Rehabilitation program included memantine and morphine treatment (added to patient's prior pain medication) and concurrent psychological and physiotherapeutic intervention. Primary outcome measure was a change in CRPS symptom count and secondary outcomes were motor performance, psychological factors, pain intensity, and quality of life. Methods Ten patients with chronic upper limb CRPS I (median 2.9 years, range 8 months to 12 years) were recruited to the study and were assessed before and after the intervention. Hand motor function of the patients was evaluated by an independent physiotherapist. There were standardized questionnaires for depression, pain anxiety, pain acceptance, quality of life, and CRPS symptom count. In addition, psychological factors were evaluated by a semi-structured interview. Severity of experienced pain was rated at movement and at rest. In addition, a video experiment of a hand action observation was conducted pre- and post-intervention to study possible change in neuronal maladaptation. Intervention consisted of pharmacological, psychological and physiotherapeutic treatment. First, 10 mg daily morphine was started and increased gradually to 30 mg daily, if tolerated. After 30 mg/day or tolerated dose of morphine was achieved, 5 mg daily memantine was started and increased gradually to 40 mg, if tolerated. Psychological intervention consisted of weekly group sessions, using cognitive and behavioral methods (relaxation, behavioral activation, and exposure) and acceptance and commitment therapy (ACT) and daily home practice. Physiotherapeutic intervention consisted of graded motor imagery and physiotherapy exercises with weekly group sessions and/or individual guidance by the physiotherapist, and individual exercise of the affected upper limb. Results Multimodal intensive intervention resulted in significant decrease in CRPS symptom count. The effect was strongest in motor and trophic symptoms (19% decrease after intervention) and in sensory symptoms (18% decrease). Additionally, improvement was seen in some, but not all, secondary outcomes (movement pain, motor symptoms, change in perceptions during video experiment of hand actions, and summary index with motor functioning, pain, and psychological factors). There were no dropouts. Conclusions Intensive 12-week multimodal intervention reduced some CRPS symptoms but was not sufficient to alter patients' rest pain, distress, or quality of life. Implications These results support the efficacy of an interdisciplinary rehabilitation program for pain and function in chronic CRPS patients. After intervention, some CRPS symptoms reduced and function improved, but distress and quality of life were unchanged. This may be due to the relatively short duration of this program; to delayed effects; to particular cognitive problems of CPRS patients; and/or to low distress levels at baseline that make statistically significant reduction less likely.
Learn More >Background and aims The co-morbidity between pain and depression is a target of interest for treatment. However most of the published literature on the topic has used clinical cohorts as the population of interest. The goal of this study was to use a nationally representative sample to explore how health outcomes varied across pain and depression status in a cohort sampled from the general US population. Methods This was a cross-sectional analysis of adults ≥18 years in the 2009-2010 National Health and Nutrition Examination Survey. The cohort was stratified into: no pain/depression, pain alone, depression alone, and pain with depression. The primary outcome was self-reported general health status, and secondary outcomes were healthcare visits, overnight hospital stays and functional limitation. Survey weighted logistic regression was used to adjust for potential confounders. Results The cohort consisted of 4,213 individuals, of which 186 (4.4%) reported concurrent pain and depression. 597 (14.2%) and 253 (6.0%) were classified with either pain or depression alone, respectively. The majority of individuals with co-morbid pain and depression reported poor health (65.1%, p<0.001) and were significantly more likely than those with neither condition to rate their health as poor after adjustment (OR: 7.77, 95% CI: 4.24-14.26, p<0.001). Those with pain only or depression only were also more likely to rate their health as poor, albeit to a lesser extent (OR: 2.21, 95% CI: 1.21-2.34, p<0.001; OR: 3.75, 95% CI: 2.54-5.54, p<0.001, respectively). A similar pattern was noted across all secondary outcomes. Most notably, those with co-morbid pain and depression were the most likely to endorse functional limitation (OR: 13.15, 95% CI: 8.00-21.61, p<0.001). Comparatively, a similar trend was noted amongst those with pain only or depression only, though with a reduced effect size (OR: 4.23, 95% CI: 3.12-4.77, p<0.001; OR: 5.13, 95% CI: 3.38-7.82, p<0.001). Conclusions Co-morbid pain and depression in the general population resulted in markedly worse outcomes versus isolated pain or depression. Further, the effect appears to be synergistic. Given the substantial burdens of pain and depression, future treatments should aim to address both conditions simultaneously. Implications As a result of the co-morbidity between pain and depression, patients presenting with either condition should increase the index of suspicion among clinicians and prompt screening for the reciprocal condition. Early intervention for co-morbid pain and depression has the potential to mitigate future incidence of chronic pain and major depression.
Learn More >To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions.
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