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Cutaneous allodynia (CA) is an abnormal pain in response to non-painful stimuli. In the present study, we sought to investigate the presence of CA, its associated factors, and its clinical implications in patients with cluster headache (CH). In this cross-sectional study, we analysed data from a prospective multicentre registry enrolling consecutive patients with CH. We identified CA during and between headache attacks using the 12-item Allodynia Symptom Checklist (ASC) administered during the CH bout period. Comorbid depression and anxiety were ascertained using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) scales. Headache impact was evaluated using the Headache Impact Test-6 (HIT-6). Of 119 eligible patients, 48 and two (40.3% and 1.7%) had CA during and between headache attacks, respectively. In univariable analyses, total CH duration, major depressive disorder (MDD), and generalized anxiety disorder (GAD) were associated with CA during headache attack. They remained significantly associated with CA during headache attack in multivariable analyses. Patients with CA during headache attack had higher headache impact (P = 0.002). A "50% responder" analysis showed no difference in outcome of acute and preventive treatment between patients with and without CA during headache attack. Patients with CH commonly experienced CA during headache attack, but not between headache attacks. CA during headache attack was associated with disease duration, depression, and anxiety.
Learn More >Using structure- and ligand-based design principles, a novel series of piperidyl chromane arylsulfonamide Na1.7 inhibitors was discovered. Early optimization focused on improvement of potency through refinement of the low energy ligand conformation and mitigation of high in vivo clearance. An in vitro hepatotoxicity hazard was identified and resolved through optimization of lipophilicity and LLE to arrive at GNE-616 (24), a highly potent, metabolically stable, subtype selective inhibitor of Na1.7. Compound 24 showed a robust PK/PD response in a Na1.7 dependent mouse model and site-directed mutagenesis was used to identify residues critical for the isoform selectivity profile of 24.
Learn More >Background and aims Chronic pelvic pain (CPP) in women is a complex condition that can seriously impact health and quality of life. Clinical guidelines for CPP place great demands on healthcare professionals, as they require both specialized knowledge about the pelvic area and knowledge of the mechanisms of chronic pain. To ensure best possible assessment and treatment of these women it is important to bring about more knowledge of the special CPP features. The purpose of this paper is to describe the characteristics of women with CPP evaluated at the University Hospital of North Norway, and further referred to physiotherapy. The frequency of having a history of abuse or previous pelvic surgery will also be reported, and analyses performed to investigate if subjective health status differs between women with and without these experiences. Methods We collected cross-sectional data from 62 women with CPP aged 20-65 (mean age 38.0), referred to physiotherapy after assessment by medical specialists. Data were collected by semi-structured interviews for demographic variables and medical history, and self-administered questionnaires on pain intensity, sexual function, urinary incontinence (UI), anal incontinence (AI), obstructed defecation syndrome (ODS), subjective health complaints (SHC) and symptoms of anxiety and depression. Results Pain duration of more than 10 years was reported by 42%, mean pain score was 4.7/10, and analgesics were used weekly by 48%. Previous pelvic or abdominal surgery was reported by 71%, and sick leave >12 weeks the last year by 34%. Reduced sexual desire was reported by 78%, dyspareunia by 73%, UI by 54%, AI by 23%, and obstructed defecation syndrome (ODS) by 34%. More than 90% reported musculoskeletal or pseudoneurologic complaints. Anxiety and depression scores defined as requiring treatment were reported by 40%. Abuse was reported by 50%, and associated with significantly more reports of ODS (p=0.02), more SHC (p=0.02) and higher anxiety scores (p=0.009). Analgesic use and sick leave were significantly higher both among women with a history of abuse (p=0.04 and p=0.005) and among those with previous surgery (p=0.04 and p=0.02). Women with previous surgery reported significantly lower pain intensity during intercourse than those without previous surgery (p=0.008). Conclusions Women with CPP have complex symptoms and high scores for both physical and psychological complaints. Women exposed to abuse have especially high scores related to analgesic use, sick leave, ODS, anxiety and SHC. Women with previous surgery report more analgesic use and sick leave, and lower pain intensity during intercourse, than those without previous surgery. Implications This study illustrates the complexity of CPP and highlights the need for health professionals to have specialized knowledge of the possible features of the condition. Previous abuse seems to be more associated with poor scores on several health outcomes than surgery, but this needs to be investigated further.
Learn More >Background and aims Chronic pain is a leading cause to years lived with disability worldwide. However, few of the interventions used in pain medicine have proven efficacy, and evidence from the existing studies may not be valid for the general pain population. Therefore, it is of utmost need that we describe chronic pain conditions in their most relevant aspects, their various guises, as well as the real world outcomes of our clinical interventions. The most obvious and crude way to make these assessments are through large registries where patient characteristics, treatment characteristics (including but not limited to what, when, how often and by whom), treatment outcomes and patient outcomes are scrutinized and recorded. Methods and results This article describes in detail the design and baseline data of the comprehensive Oslo University Hospital Pain Registry (OPR). OPR is the local registry of the largest university and interdisciplinary outpatient pain clinic in Norway. Data registration started in October 2015, and approximately 1,000 patients are assessed and treated at the clinic each year. During the first 2 years of running the OPR (through September 2017), a total of 1,712 patient baseline reports were recorded from 2,001 patients. Clinicians enter data about relevant treatments and interventions, while patients provide self-reported data on aspects related to pain and pain management. The patients complete an electronic registration immediately before their first consultation at the outpatient pain clinic. The baseline questions of the OPR cover: Basic demographics; The Modified Oswestry Disability Index to assess general function; A pain drawing to assess pain location; Questions regarding the temporal aspects of pain; Six 0-10 Numeric Rating Scales to assess pain intensity and bothersomeness; The EQ-5D-5L to measure health-related quality of life; The Hopkins Symptom Check List-25 to assess psychological distress; A single question about self-rated health; The general self-efficacy scale to assess the patient's perceived self-efficacy; The Bodily Distress Syndrome checklist to assess functional disorders; The Injustice Experience Questionnaire to assess whether the patients experience injustice; Chalder Fatigue Questionnaire to assess fatigue; The Insomnia Severity Index to assesses the levels of insomnia symptoms; The Pain Catastrophizing Scale to measure pain catastrophizing and exaggerated negative orientation toward pain stimuli and pain experience; And the SF36v2 to assess patients' self-report of generic health and wellbeing. The baseline data show that chronic pain patients have a high degree of negative impact in all aspects of their lives. Conclusions and implications The OPR is the most comprehensive pain registry for multidisciplinary and interdisciplinary outpatient pain clinics in Norway. Detailed design of the registry and key baseline data are presented. Registries are of great value in that they enable real world effectiveness outcomes for patients with chronic pain conditions. The OPR can thus serve as a model for similar initiatives elsewhere. The OPR cohort may also serve as a historical control in future studies, both with experimental and observational design.
Learn More >Background and aims While the Nordic countries have considerably stricter controls on opioid prescribing for chronic non-cancer pain than other countries, previous research has warned that prescription of strong opioids is increasing. This study examines consumption of and developments in dispensed prescribed opioids to individuals receiving ambulatory care from 2006 to 2017, using publicly available data from each of three Nordic countries' national prescription registries. Methods Repeated, cross-sectional design. One-year prevalence of all dispensed prescribed opioids in ATC N02A group were reported for Norway, Denmark, and Sweden in the period 2006-2017 by gender. One-year prevalence of the weak opioids tramadol and codeine and the strong opioid oxycodone were then reported separately over this period for each country. The mean defined daily dose (DDD) per user per year, an estimate of the amount of opioids prescribed, was reported for each of the three opioids in 2016. Results Patterns of dispensed prescribed opioids differ greatly between 2006 and 2017 and between countries, with tramadol increasing in Norway, codeine declining across the board, and oxycodone increasing in all three countries. Norway exceeded Sweden and Denmark in prevalence of all dispensed prescribed opioids, with 12.1% of the female Norwegian population and 9.2% of the male Norwegian population dispensed at least one prescribed opioid as an outpatient in 2016. Norway's high overall prevalence rates are tempered by dispensing the lowest mean doses of both weak opioids compared to Sweden. Similarly, Sweden dispenses the lowest mean doses of oxycodone but to the largest proportion of its population (3.0%). Conclusions Significant shifts have occurred in the dispensing of prescribed opioids in Norway, Sweden, and Denmark over the past 12 years. The increasing prevalence of oxycodone in all three countries should continue to be monitored. Prescription registries provide a wealth of publicly available data that can be used to monitor and to guide prescribing policies in a more knowledge-based direction.
Learn More >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.
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