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Cognitive Impairment in a Classical Rat Model of Chronic Migraine may be due to Alterations in Hippocampal Synaptic Plasticity and NMDA Receptor Subunits.

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.

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Literature review and methodological considerations for understanding circulating risk biomarkers following trauma exposure.

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.

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The role of perioperative ketamine in postoperative pain control following spinal surgery.

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.

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Emotion regulation as a transdiagnostic factor underlying co-occurring chronic pain and problematic opioid use.

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).

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Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset.

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.

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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.

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Patient race and opioid misuse history influence provider risk perceptions for future opioid-related problems.

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).

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Moderated mediation for exercise maintenance in pain and posttraumatic stress disorder: A randomized trial.

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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Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

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The relative contribution of pain and psychological factors to opioid misuse: A 6-month observational study.

There is a pressing need to better understand the factors contributing to prescription opioid misuse among patients with chronic pain. Cross-sectional studies have been conducted in this area, but longitudinal studies examining the determinants of prescription opioid misuse repeatedly over the course of opioid therapy have yet to be conducted. The main objective of this study was to examine the relative contribution of pain and psychological factors to the occurrence of opioid misuse among patients with chronic pain prescribed opioids. Of particular interest was to examine whether pain intensity and psychological factors were more strongly associated with certain types of opioid misuse behaviors. Patients with chronic pain (n = 194) prescribed long-term opioid therapy enrolled in this longitudinal observational cohort study. Patients completed baseline measures and were then followed for 6 months. Opioid misuse was assessed once a month using self-report measures, and urine toxicology screens complemented patients' reports of opioid misuse. Heightened pain intensity levels were associated with a greater likelihood of opioid misuse (p = .014). However, pain intensity was no longer significantly associated with opioid misuse when controlling for psychological factors (i.e., negative affect, catastrophizing). Subsequent analyses revealed that higher levels of catastrophizing were associated with a greater likelihood of running out of opioid medication early, even after controlling for patients' levels of pain intensity and negative affect (p = .016). Our findings provide new insights into the determinants of prescription opioid misuse and have implications for the nature of interventions that may be used to reduce specific types of opioid misuse behaviors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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