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Patient reported outcomes and neuropsychological testing in patients with chronic non-cancer pain in long-term opioid therapy: a pilot study.

Background and aims Opioid consumption has increased dramatically in patients with chronic non-cancer pain (CNCP), but long-term consequences are still unclear. The aim of this study is to investigate the effects of long-term opioid treatment on pain, cognition, mood, sleep and quality of life in CNCP patients. Methods In this cross-sectional pilot study, two groups of patients with CNCP treated in a multidisciplinary pain center were selected: (1) opioid group: ≥30 mg morphine equivalent/day for >4 weeks, and (2) control group: no opioid consumption for >4 weeks. Socio-demographic data, alcohol consumption, smoking habits and body mass index (BMI) were registered and pain (brief pain inventory), mood (Hospital Anxiety and Depression Scale), sleep (Pittsburgh Sleep Quality Index) and quality of life (RAND 36-Item Health Survey) were assessed. Continuous Reaction Time and the Digit Span Test were used to evaluate cognitive function. Data was analyzed with a Fisher's exact test and Wilcoxon two-sample test. Results Forty-two patients with CNCP were included (21 in each group). No differences regarding socio-demographics, smoking/alcohol habits and duration, type, or intensity of pain were found. More patients in the opioid group had significantly higher BMI (62% above BMI 25 vs. 33.3%, p = 0.042). Consequently, the subsequent data analyses were controlled for BMI. The two groups did not differ in pain, cognition, anxiety, depression, sleep or quality of life but both showed lower values than the normal standards. Further, the opioid group presented a tendency to lower ratings regarding pain and social function and performed below the normal cut off in the continuous reaction time. Conclusions No significant differences between the two groups were found regarding any of the above-mentioned variables. Interestingly, the patients assessed, regardless of taking opioids or not, could be classified with moderate pain intensity, anxiety and low quality of sleep and life compared to norm standards. Implications The findings of this pilot study suggested that long-term opioid treatment may influence pain and quality of life among CNCP patients. A larger cohort is needed to verify these findings.

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Lessons learned from piloting a pain assessment program for high frequency emergency department users.

Background and aims Chronic pain (CP) management presents a challenge for the healthcare system as many individuals experiencing CP cannot access appropriate services. Consequently, individuals may visit emergency departments (EDs) to address their CP, even though this setting is not the most appropriate. CP was identified as a common factor amongst patients with repeat ED use at a hospital in Ottawa, Canada. Thus, staff of the Pain Clinic developed the Rapid Interdisciplinary Pain Assessment Program to improve the care of patients with CP who had a minimum of 12 ED visits in the previous year, who were considered high frequency users (HFUs) of the ED. This evaluation was conducted to guide program improvements in advance of a clinical trial. The results are reported here in order to describe lessons that could be applied to the development of similar programs. The benefits of the program in reducing ED use, pain intensity, disability, and psychological distress have been described elsewhere (Rash JA et al. Pain Res Manag 2018:1875967). Methods Thirty-five people completed semi-structured interviews or a focus group, including eight patients, six ED staff, four primary care physicians (PCP), five Pain Clinic physicians, and 12 program staff members. Questions focused on the program's implementation, as well as strengths and areas for improvement. Results The program was generally consistent in offering the intended patients the services that were planned. Specifically, patients received an interdisciplinary assessment that informed the development of an assessment and treatment plan. These plans were shared with the PCP and added to the patient's hospital electronic medical record. Patients also received education about CP and had access to medical pain management, substance use, and psychological treatments. Inter-professional communication was facilitated by case conferences. Numerous aspects of the program were perceived as helpful, such as the quick access to services, the comprehensive assessment and treatment plans, the individualized treatment, the use of an interdisciplinary approach to care, and the communication and relationships with other care providers. However, challenges arose with respect to the coordination of services, the addition of supplementary services, the accessibility of the program, patients' perceptions of being misunderstood, communication, and relationship-building with other service providers. Conclusions The program sought to improve the care of HFUs with CP and reduce their ED use for CP management. The program had numerous strengths, but also encountered challenges. Developers of programs for HFUs with CP are encouraged to consider these challenges and suggested solutions. These programs have the potential to deliver effective healthcare to individuals with CP and reduce ED overutilization. Implications Our findings suggest that the following points should be considered in the development of similar programs: the inclusion of a case manager; the use of strategies to ensure inter-professional communication, such as secure electronic consultation, approaches to allow access to assessment and treatment plans, and offering a range of modalities for communication; holding regular case conferences; determining the appropriate types of services to offer; and working to address patients' fears of being labelled.

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Resolvin D3 controls mouse and human nociceptive functions and preclinical progression of psoriasis.

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Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain.

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Distinct roles for innexin gap junctions and hemichannels in mechanosensation.

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BAM8-22 and its receptor MRGPRX1 may attribute to cholestatic pruritus.

Pruritus is an unexpected symptom observed in cholestasis and its mechanism is still unclear. Here, we show that bovine adrenal medulla (BAM) 8-22, an endogenous itch-inducing peptide, could be involved in cholestatic pruritus. It was found that bile duct ligation (BDL) mice, an obstructive cholestasis model, showed increased spontaneous scratching behaviour. Importantly, the mRNA level of proenkephalin, a precursor polypeptide of BAM8-22, was significantly increased in the skin of BDL mice. Furthermore, the mRNA level of Mrgprx1, which encodes a receptor for BAM8-22, was significantly increased in the dorsal root ganglia (DRG) of BDL mice. This was further confirmed by elevation of intracellular calcium levels upon BAM8-22 treatment in primarily-cultured DRG neurons. In addition, BDL mice showed augmented scratching behaviour by BAM8-22, indicating enhanced activity of MRGPRX1. Moreover, the skin homogenate of BDL mice induced elevation of intracellular calcium levels through MRGPRX1. Finally, among the various bile acids, chenodeoxycholic acid significantly increased proenkephalin transcription in a human keratinocyte cell line (HaCaT). In conclusion, cholestatic pruritus could be attributed in part to enhanced action of both BAM8-22 in the skin and its receptor MRGPRX1 in sensory neurons.

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Demographic, clinical, and treatment characteristics of the juvenile primary fibromyalgia syndrome cohort enrolled in the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

To describe the demographic, clinical, and treatment characteristics of youth diagnosed with juvenile primary fibromyalgia syndrome (JPFS) who are seen in pediatric rheumatology clinics.

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Test-retest repeatability of questionnaire for pain symptoms for school children aged 10-15 years.

Background and aims There is a growing body of evidence, that pain is common at school age. Less is known about the repeatability of pain questionnaires for children. This study aimed to assess the test-retest repeatability of the Finnish version of the electronic pain questionnaire for school-aged children. Methods Primary (n = 79) and lower secondary (n = 127) schoolchildren aged 10-15 years from two schools from the Jyväskylä region of Finland, filled in an electronic questionnaire twice in an interval of 2 weeks. It captured the frequency of pain symptoms with a five-point Likert-scale questionnaire covering nine areas of the body for the last 3 months. The intraclass correlation coefficient (ICC) values 0.40-0.59 reflected fair and 0.60-0.74 good repeatability. Results The highest prevalences of pain were in the head (29%) and neck and shoulder (NS) (23%) areas. ICC values showed good repeatability for questions about pain frequency in the head, NS and lower extremities. In primary school, these values were good in the lower extremities and fair in NS, lower back and the head. In lower secondary school, the ICC values were good in NS and the head, fair in the stomach and lower extremities. Conclusions This electronic questionnaire was an acceptably repeatable indicator to measure the frequency of pain in the most prevalent pain areas: the head and NS. Implications It is important to be aware of the impact of health-related outcomes on children's ability to be successful in their lives. With the help of a simple electronic questionnaire, it is possible to cost-effectively capture, for example, the prevalence and frequency of pain during the school hours. The identification of children's pain symptoms accurately provides more possibilities to prevent and to minimize the chronic pain among schoolchildren.

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Psychological factors can cause false pain classification on painDETECT.

Background and aims The painDETECT questionnaire (PD-Q) has been widely used as a screening tool for the identification of neuropathic pain (NeP) as well as a tool for the characterization of patients' pain profile. In contrast to other NeP screening tools, the PD-Q is the only screening tool with weighted sensory descriptors. It is possible that responses to the PD-Q sensory descriptors are influenced by psychological factors, such as catastrophizing or anxiety, which potentially might contribute to an overall higher score of PD-Q and a false positive identification of NeP. This study aimed to explore (i) the relationship between psychological factors (catastrophizing, anxiety, depression and stress) and the total PD-Q score and (ii) if psychological factors are associated with false positive identifications of NeP on the PD-Q compared to clinically diagnosed NeP. Methods The study was a retrospective review of 1,101 patients attending an outpatient pain centre. Patients were asked to complete the PD-Q, the Pain Catastrophizing Scale (PCS), the Depression, Anxiety and Stress Scale (DASS) and the Brief Pain Inventory (BPI). For patients who were identified by PD-Q as having NeP, their medical records were reviewed to establish if they had a clinical diagnosis of NeP. Results Accounting for missing data, complete datasets of 652 patients (mean age 51 (SD14) years, range 18-88; 57% females) were available for analysis. Based on PD-Q scoring, NeP was likely present in 285 (44%) patients. Depression, anxiety, stress, catastrophizing, BPI pain and BPI interference were all significantly related to each other (p < 0.0001) and patients displaying these traits were significantly more likely to have a positive PD-Q score (p < 0.0001). For patients classified by PD-Q as having NeP, only 50% of patients had a clinical diagnosis of NeP. Anxiety was significantly associated with a false positive classification of NeP on PD-Q (p = 0.0036). Conclusions Our retrospective study showed that psychological factors including catastrophizing, depression, anxiety, and stress were all influential in producing a higher score on the PD-Q. We observed a high rate of false positive NeP classification which was associated with the presence of anxiety. Implications Clinicians and researchers should be aware that a patient's psychological state may influence the responses to PD-Q and consequently the final PD-Q score and its NeP classification.

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Field testing of the revised neuropathic pain grading system in a cohort of patients with neck and upper limb pain.

Background and aims In 2008, the International Association for the Study of Pain Special Interest Group on Neuropathic Pain (NeuPSIG) proposed a clinical grading system to help identify patients with neuropathic pain (NeP). We previously applied this classification system, along with two NeP screening tools, the painDETECT (PD-Q) and Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS), to identify NeP in patients with neck/upper limb pain. Both screening tools failed to identify a large proportion of patients with clinically classified NeP, however a limitation of our study was the use of a single clinician performing the NeP classification. In 2016, the NeuPSIG grading system was updated with the aim of improving its clinical utility. We were interested in field testing of the revised grading system, in particular in the application of the grading system and the agreement of interpretation of clinical findings. The primary aim of the current study was to explore the application of the NeuPSIG revised grading system based on patient records and to establish the inter-rater agreement of detecting NeP. A secondary aim was to investigate the level of agreement in detecting NeP between the revised NeuPSIG grading system and the LANSS and PD-Q. Methods In this retrospective study, two expert clinicians (Specialist Pain Medicine Physician and Advanced Scope Physiotherapist) independently reviewed 152 patient case notes and classified them according to the revised grading system. The consensus of the expert clinicians' clinical classification was used as "gold standard" to determine the diagnostic accuracy of the two NeP screening tools. Results The two clinicians agreed in classifying 117 out of 152 patients (ICC 0.794, 95% CI 0.716-850; κ 0.62, 95% CI 0.50-0.73), yielding a 77% agreement. Compared to the clinicians' consensus, both LANSS and PD-Q demonstrated limited diagnostic accuracy in detecting NeP (LANSS sensitivity 24%, specificity 97%; PD-Q sensitivity 53%, specificity 67%). Conclusions The application of the revised NeP grading system was feasible in our retrospective analysis of patients with neck/upper limb pain. High inter-rater percentage agreement was demonstrated. The hierarchical order of classification may lead to false negative classification. We propose that in the absence of sensory changes or diagnostic tests in patients with neck/upper limb pain, classification of NeP may be further improved using a cluster of clinical findings that confirm a relevant nerve lesion/disease, such as reflex and motor changes. The diagnostic accuracy of LANSS and PD-Q in identifying NeP in patients with neck/upper limb pain remains limited. Clinical judgment remains crucial to diagnosing NeP in the clinical practice. Implications Our observations suggest that in view of the heterogeneity in patients with neck/upper limb pain, a considerable amount of expertise is required to interpret the revised grading system. While the application was feasible in our clinical setting, it is unclear if this will be feasible to apply in primary health care settings where early recognition and timely intervention is often most needed. The use of LANSS and PD-Q in the identification of NeP in patients with neck/upper limb pain remains questionable.

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