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Voltage-gated sodium channel Nav1.7 has been validated as a perspective target for selective inhibitors with analgesic and anti-itch activity. The objective of this study was to discover new candidate compounds with Nav1.7 inhibitor properties. The authors hypothesized that their approach would yield at least one new compound that inhibits sodium currents in vitro and exerts analgesic and anti-itch effects in mice.
Learn More >Chronic pain and opioid misuse occur in pediatric populations and can be associated with a range of negative adverse outcomes that may persist into adulthood. While the association between chronic pain, opioid prescribing, and opioid-related adverse consequences is reasonably well established in adults, the relation in pediatric patients is not well understood and the long-term impact of opioid exposure during childhood is yet to be fully revealed. The present review draws from the available literature on chronic and acute pediatric pain prevalence and treatment, opioid misuse, and adolescent substance use to address knowns and unknowns of comorbid pediatric chronic pain and opioid misuse. Additionally, gaps in knowledge regarding the prevalence and etiology of co-occurring chronic pain and opioid misuse in youth are identified. Hypothesized, modifiable risk factors associated with both pediatric pain and opioid misuse are considered. Due to a lack of empirically supported integrated treatments for comorbid chronic pain and opioid misuse in youth, this review examines the evidence base and best practices from both the chronic pain and opioid treatment literature to guide treatment recommendations for these comorbid conditions in youth. Recommendations are then provided to promote screening and mitigate risk of chronic pain and opioid misuse across a range of pediatric settings. Lastly, a comprehensive agenda to prevent and treat chronic pain and opioid misuse in adolescents and young adults is discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Learn More >Although migraine is a major global public health problem, its impact on cognitive abilities remains controversial. Thus, the present study investigated the effects of repeated administration of inflammatory soup (IS) to the dura of rats, over 3 weeks, on spatial cognition, hippocampal synaptic plasticity, and the expression of N-methyl-D-aspartate receptor (NMDAR) subunits. Additionally, low doses of amitriptyline (AMI; 5 mg/kg) were applied to assess its therapeutic effects. The IS group exhibited significant reductions in the cutaneous stimulation threshold, presence of mild cognitive impairment, and decreased long-term potentiation (LTP) in right hippocampus. However, AMI improved pain behaviors, enhanced cognitive function, and increased synaptic plasticity in the IS rats. On the other hand, the administration of AMI to normal rats negatively influenced synaptic plasticity and reduced the expression of NMDAR subunits. The present results indicate that IS-induced dural nociception led to impairments in spatial cognition that could be attributed to reductions in hippocampal LTP and the decreased expression of NMDAR subunits.
Learn More >Exposure to traumatic events is common. While many individuals recover following trauma exposure, a substantial subset develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as posttraumatic stress, major depression, and regional or widespread chronic musculoskeletal pain. APNS cause substantial burden to the individual and to society, causing functional impairment and physical disability, risk for suicide, lost workdays, and increased health care costs. Contemporary treatment is limited by an inability to identify individuals at high risk of APNS in the immediate aftermath of trauma, and an inability to identify optimal treatments for individual patients. Our purpose is to provide a comprehensive review describing candidate blood-based biomarkers that may help to identify those at high risk of APNS and/or guide individual intervention decision-making. Such blood-based biomarkers include circulating biological factors such as hormones, proteins, immune molecules, neuropeptides, neurotransmitters, mRNA, and noncoding RNA expression signatures, while we do not review genetic and epigenetic biomarkers due to other recent reviews of this topic. The current state of the literature on circulating risk biomarkers of APNS is summarized, and key considerations and challenges for their discovery and translation are discussed. We also describe the AURORA study, a specific example of current scientific efforts to identify such circulating risk biomarkers and the largest study to date focused on identifying risk and prognostic factors in the aftermath of trauma exposure.
Learn More >Opioid abuse has rapidly developed into an epidemic across the United States. Patients are often introduced to opioids following surgical procedures-this is particularly relevant following spinal surgery. Surgeons can help reduce this opioid burden by finding alternatives to narcotic analgesia in the postoperative period. One such medication that has shown potential in this role is ketamine, which has been studied in various surgical specialties. A review was performed of current literature regarding ketamine use in the perioperative period specific to spinal surgery. This review focused on prospective randomized control trials; the primary endpoint was opioid consumption in the postoperative period, monitored through patient-controlled analgesia (PCA) use. Both pediatric and adult spinal surgery patients were included; cervical, thoracic, and lumbar procedures were also all included. 10 studies were selected for this reviewed based on inclusion criteria, published between 2004 and 2017. 7 of these studies demonstrated a significant decrease in postoperative opioid use with the integration of ketamine in the perioperative period, while 3 trials showed no significant difference in opioid consumption. There is inherent difficulty in standardizing studies of this nature-dosing protocols, medication timing, and supplemental analgesia were variable throughout the included studies. However, this review of the most up-to-date prospective studies indicate ketamine has potential to play a significant role in reducing opioid requirements following spinal surgery, and further study is warranted in this field.
Learn More >Chronic pain is a common and costly condition, and some people with chronic pain engage in problematic opioid use. There is a critical need to identify factors underlying this co-occurrence, so that treatment can be targeted to improve outcomes. We propose that difficulty with emotion regulation (ER) is a transdiagnostic factor that underlies the co-occurrence of chronic pain and problematic opioid use (CP-POU). In this narrative review, we draw from prominent models of ER to summarize the literature characterizing ER in chronic pain and CP-POU. We conclude that chronic pain is associated with various ER difficulties, including emotion identification and the up- and down-regulation of both positive and negative emotion. Little research has examined ER specifically in CP-POU; however, initial evidence suggests CP-POU is characterized by difficulties with ER that are similar to those found in chronic pain more generally. There is great potential to expand the treatment of ER to improve pain-related outcomes in chronic pain and CP-POU. More research is needed, however, to elucidate ER in CP-POU and to determine which types of ER strategies are optimal for different clinical presentations and categories of problematic opioid use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Learn More >Despite the widespread use, only sparse information is available on the safety of gabapentin during pregnancy. We sought to evaluate the association between gabapentin exposure during pregnancy and risk of adverse neonatal and maternal outcomes.
Learn More >Pain prevention and management must begin in childhood: the key role of psychological interventions.
Pain conditions in childhood often continue into adulthood. Childhood chronic pain is related to a range of vulnerabilities that may have contributed to the onset of childhood pain or that may co-occur as a consequence of childhood pain. These vulnerabilities have been shown to maintain pain and disability during childhood but may also contribute to long-term developmental and health impairments that affect adult life. If progress is to be made in reducing the impact of pain and disability through the lifespan, greater efforts need to be directed toward understanding why, for whom, and how pain occurring in childhood affects subsequent adult pain and health. In this review, a developmental framework is applied to link childhood pain to adult pain highlighting childhood vulnerabilities (emotional, health behavior, social/family, and neurobiological) that may represent pathways for interventions in childhood to interrupt this trajectory. Psychological interventions can play a key role in addressing childhood pain and vulnerabilities associated with risk for maladaptive adult outcomes. The review summarizes the evidence base for the effectiveness of psychological interventions for childhood chronic pain and identifies gaps and opportunities to further develop and test early targeted interventions in childhood to reduce childhood chronic pain as well as build resiliency to promote positive adult outcomes. A future research agenda is delineated including the need for longitudinal cohort studies from childhood into adulthood and testing of both targeted early intervention to reduce risk and build resiliency to enhance long-term adult pain, health, developmental, and social outcomes.
Learn More >In response to the dual public health crises of chronic pain and opioid use, providers have become more vigilant about assessing patients for risk of opioid-related problems. Little is known about how providers are making these risk assessments. Given previous studies indicating that Black patients are at increased risk for suboptimal pain care, which may be related to stereotypes about drug abuse, the current study examined how patient race and previous opioid misuse behaviors impact providers' risk assessments for future prescription opioid-related problems. Physician residents and fellows (N = 135) viewed videos and read vignettes about 8 virtual patients with chronic pain who varied by race (Black/White) and history of prescription opioid misuse (absent/present). Providers rated patients' risk for future prescription opioid-related adverse events, misuse/abuse, addiction, and diversion, and also completed measures of implicit racial attitudes and explicit beliefs about race differences in pain. Two significant interactions emerged indicating that Black patients were perceived to be at greater risk for future adverse events (when previous misuse was absent) and diversion (when previous misuse was present). Significant main effects indicated that Black patients and patients with previous misuse were perceived to be at greater risk for future misuse/abuse of prescription opioids, and that patients with previous misuse were perceived to be at greater risk of addiction. These findings suggest that racial minorities and patients with a history of prescription opioid misuse are particularly vulnerable to any unintended consequences of efforts to stem the dual public health crises of chronic pain and opioid use. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Learn More >This study utilizes the Science of Behavior Change (SOBC) experimental medicine approach to evaluate the effects of a 3-month, individually prescribed progressive exercise training program on neurobiological, cognitive and motivational mechanisms by which our exercise-training paradigm may foster exercise maintenance. We will investigate hypothesized relationships between exercise-training associated augmentation of neuropeptide Y (NPY) system function and improvements in self-regulation and reward sensitivity-cognitive control and motivational processes posited to promote self-efficacy and intrinsic motivation, which have been shown to predict exercise maintenance. This study will recruit Veterans with chronic low back pain and posttraumatic stress disorder (PTSD). Procedures include a baseline, acute cardiopulmonary exercise challenge assessment that will inform the exercise prescription for a 12-week progressive exercise training program comprised of three 45-minute aerobic exercise sessions per week-all of which will be supervised by an exercise physiologist. Additionally, a week-7 and week-14 exercise challenge assessment will track changes in NPY system function and the variables of interest. We hypothesize that increases in the capacity to release NPY in response to acute exercise testing will be associated with improvements in self-regulation and reward sensitivity, which will in turn be associated with self-efficacy and intrinsic motivation to maintain regular exercise. Ninety participants will be randomized either to the "active exercise training condition" or to the "wait list symptom monitoring condition". The study aims to demonstrate the feasibility of procedures and elucidate mechanisms relevant to developing individually prescribed, motivationally based exercise regimens to reduce negative consequences of PTSD and low back pain over the long-term. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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