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Treatment Strategies and Effective Management of Phantom Limb-Associated Pain.

Phantom sensations are incompletely understood phenomena which take place following an amputation or deafferentation of a limb. They can present as kinetic, kinesthetic, or exteroceptive perceptions. It is estimated that phantom limb pain (PLP) affects anywhere from 40 to 80% of amputees.

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Spinal and afferent PKC signaling mechanisms that mediate chronic pain in sickle cell disease.

Pain is the most characteristic feature of sickle cell disease (SCD). Patients with SCD live with unpredictable, recurrent episodes of acute painful crisis, as well as chronic unremitting pain throughout their lifetime. While most of the research and medical efforts have focused on treating vaso-occlusion crisis and acute pain, chronic pain remains a significant challenge faced by patients and physicians. Emerging evidence from human and animal studies has suggested the presence of a neuropathic component in SCD pain. New knowledge on the neurobiology of chronic pain in SCD has significant implications in unraveling the underlying mechanisms. This review focuses on the recent advances on the role of protein kinase C or PKC in promoting and maintaining chronic pain conditions. With a highlight of a specific PKC isoform, PKCδ, we aim to propose PKC as an essential regulator of chronic pain in SCD, which may ultimately lead to innovative therapeutic strategies for treating this devastating life-long problem in patients with SCD.

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Uncoupling sodium channel dimers rescues phenotype of pain-linked Nav1.7 mutation.

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Predicting chronic pain after major traumatic injury.

Background and aims Chronic pain after traumatic injury and surgery is highly prevalent, and associated with substantial psychosocial co-morbidities and prolonged opioid use. It is currently unclear whether predicting chronic post-injury pain is possible. If so, it is unclear if predicting chronic post-injury pain requires a comprehensive set of variables or can be achieved only with data available from the electronic medical records. In this prospective study, we examined models to predict pain at the site of injury 3-6 months after hospital discharge among adult patients after major traumatic injury requiring surgery. Two models were developed: one with a comprehensive set of predictors and one based only on variables available in the electronic medical records. Methods We examined pre-injury and post-injury clinical variables, and clinical management of pain. Patients were interviewed to assess chronic pain, defined as the presence of pain at the site of injury. Prediction models were developed using forward stepwise regression, using follow-up surveys at 3-6 months. Potential predictors identified a priori were: age; sex; presence of pre-existing chronic pain; intensity of post-operative pain at 6 h; in-hospital opioid consumption; injury severity score (ISS); location of trauma, defined as body region; use of regional analgesia intra- and/or post-operatively; pre-trauma PROMIS Depression, Physical Function, and Anxiety scores; in-hospital Widespread Pain Index and Symptom Severity Score; and number of post-operative non-opioid medications. After the final model was developed, a reduced model, based only on variables available in the electronic medical record was run to understand the "value add" of variables taken from study-specific instruments. Results Of 173 patients who completed the baseline interview, 112 completed the follow-up within 3-6 months. The prevalence of chronic pain was 66%. Opioid use increased from 16% pre-injury to 28% at 3-6 months. The final model included six variables, from an initial set of 24 potential predictors. The apparent area under the ROC curve (AUROC) of 0.78 for predicting pain 3-6 months was optimism-corrected to 0.73. The reduced final model, using only data available from the electronic health records, included post-surgical pain score at 6 h, presence of a head injury, use of regional analgesia, and the number of post-operative non-opioid medications used for pain relief. This reduced model had an apparent AUROC of 0.76, optimism-corrected to 0.72. Conclusions Pain 3-6 months after trauma and surgery is highly prevalent and associated with an increase in opioid use. Chronic pain at the site of injury at 3-6 months after trauma and surgery may be predicted during hospitalization by using routinely collected clinical data. Implications If our model is validated in other populations, it would provide a tool that can be easily implemented by any provider with access to medical records. Patients at risk of developing chronic pain could be selected for studies on preventive strategies, thereby concentrating the interventions to patients who are most likely to transition to chronic pain.

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Possible inflammatory pain biomarkers in postamputation pain.

Although chronic pain after amputation is frequent, the underlying mechanisms are still not well understood. It is widely accepted that the pathogenesis of postamputation pain is multifactorial, with both peripheral and central mechanisms playing an essential role. However, recent studies suggest that the immune system plays an important role in different neuropathic pain conditions, including postamputation pain. Eleven amputees were included in this clinical study. Information on the type and intensity of spontaneous postamputation pain was obtained and evoked pain responses for brush, cold, and warm allodynia and pinprick hyperalgesia were determined. In addition, skin biopsies were taken from the amputated site and a contralateral control site and analysed for possible markers of pain: IbA1 (macrophages), calcitonin gene-related peptide (CGRP), and substance P (SP). Irrespectively of the type and intensity of postamputation pain, no differences were found in IbA1, CGRP, and SP levels between the amputated site and the control site. Although no differences between the sites were seen in this study, this new method seems promising for our understanding of skin changes in amputees. In future studies, staining for other cytokines and inflammatory mediators in skin biopsies could provide new insight into the mechanisms of postamputation pain.

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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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