ng for Nav1.6, Nav1.7, and CGRP correlated with positive outcomes to topical lidocaine treatment. Epidermal keratinocytes modulate the signaling of IENF, and several analgesic and algesic signaling systems have been identified. These results further implicate epidermal signaling mechanisms as modulators of neuropathic pain conditions, highlight a novel potential mode of action for topical treatments, and demonstrate the utility of comprehensive skin biopsy evaluation to identify novel biomarkers in clinical pain studies.Background Fibromyalgia (FM) is a chronic primary pain condition, associated with widespread musculoskeletal pain, disturbed sleep, fatigue, cognitive dysfunction, and a range of comorbid conditions such as irritable bowel syndrome, and depression. Despite its high prevalence of 2% in the general population, FM continues to pose scientific and clinical challenges in definition, etiology, and day-to-day management. In terms of treatment, FM can be treated with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs). Objective Patients with FM and other chronic primary pain syndromes are known to experience substantial and clinically relevant placebo effects. An update of the placebo responses for various outcomes in the FM population and especially a discussion about clinical implications is therefore needed. Methods We used data from a large data pool that includes randomized controlled trials (RCTs) examining within-placebo mean change scores of baseline vs. follow-up assessments in FM trials of SSRIs and SNRIs. The primary outcomes were pain, functional disability, and depression and using different scales. We assessed heterogeneity of included trials. Results A total of 29 RCTs with N = 8,453 patients suffering from FM were included in our analysis. Within-placebo mean change scores of baseline vs. follow-up assessments were large for pain (mean change = 2.31, 95% CI 0.42-4.21, p = 0.017), functional disability (mean change = 3.31, 95% CI 2.37-4.26, p less then 0.000), and depression (mean change = 1.55, 95% CI 0.92-2.18, p less then 0.000). Heterogeneity was found to be large for all outcomes. Impact Our results provide preliminary evidence that placebo responses, which also consist of non-specific effects, might play a role in the treatment of FM. Furthermore, we highlight limitations of our analyses and make suggestions for future studies.Pain relief, or a decrease in self-reported pain intensity, is frequently the primary outcome of pain clinical trials. Investigators commonly report pain relief in one of two ways using raw units (additive) or using percentage units (multiplicative). However, additive and multiplicative scales have different assumptions and are incompatible with one another. In this work, we describe the assumptions and corollaries of additive and multiplicative models of pain relief to illuminate the issue from statistical and clinical perspectives. First, we explain the math underlying each model and illustrate these points using simulations, for which readers are assumed to have an understanding of linear regression. Next, we connect this math to clinical interpretations, stressing the importance of statistical models that accurately represent the underlying data; for example, how using percent pain relief can mislead clinicians if the data are actually additive. These theoretical discussions are supported by empirical data from four longitudinal studies of patients with subacute and chronic pain. Finally, we discuss self-reported pain intensity as a measurement construct, including its philosophical limitations and how clinical pain differs from acute pain measured during psychophysics experiments. This work has broad implications for clinical pain research, ranging from statistical modeling of trial data to the use of minimal clinically important differences and patient-clinician communication.Chronic pain imposes a significant burden to the healthcare system and adversely affects patients’ quality of life. Traditional subjective assessments, however, do not adequately capture the complex phenomenon of pain, which is influenced by a multitude of factors including environmental, developmental, genetic, and psychological. Quantitative sensory testing (QST), established as a protocol to examine thermal and mechanical sensory function, offers insight on potential mechanisms contributing to an individual’s experience of pain, by assessing their perceived response to standardized delivery of stimuli. Although the use of QST as a research methodology has been described in the literature in reference to specific pain populations, this manuscript details application of QST across a variety of chronic pain conditions. Specific conditions include lower extremity chronic pain, knee osteoarthritis, chronic low back pain, temporomandibular joint disorder, and irritable bowel syndrome. Furthermore, we describe the use of QST in placebo/nocebo research, and discuss the use of QST in vulnerable populations such as those with dementia. We illustrate how the evaluation of peripheral sensory nerve function holds clinical promise in targeting interventions, and how using QST can enhance patient education regarding prognostic outcomes with particular treatments. Incorporation of QST methodology in research investigations may facilitate the identification of common mechanisms underlying chronic pain conditions, guide the development of non-pharmacological behavioral interventions to reduce pain and pain-related morbidity, and enhance our efforts toward reducing the burden of chronic pain.Background The COVID-19 pandemic, a disease caused by Sars-CoV-2, has become a worldwide stressor, especially as it represents a new viral infection, which spreads quickly and easily, without prior knowledge about vaccination, and absence, to this moment, of a medication that is totally effective against the disease. Objective The aim of this observational study was to provide a general evaluation, through a questionnaire applied to students in the health field of the Federal University of Rio de Janeiro, on the psychological impacts and behavioral changes generated by the COVID-19 pandemic on oral health, especially the triggering or exacerbation of bruxism and temporomandibular disorders (TMD). Methods In order to verify the impacts of the pandemic on the health of UFRJ healthcare students, a non-randomized survey was performed with 370 students. Results It was found that 72% of the students had their sleep routine altered, 65% had greater difficulty in keeping their spirits up, there was a statistically significant increase in emotional stress, headaches, and daytime teeth clenching. Conclusion It was possible to conclude that the outbreak of COVID-19 resulted in psychological, physiological and behavioral impacts on students.Pain is a common symptom in cancer patients, restricts daily life activities and reduces survival time. Identification of sociodemographic, medical and psychological correlates of pain among cancer patients in Germany could help identify subgroups most in need of pain management. In this multicenter, epidemiologic cross-sectional study, we assessed pain prevalence and severity, quality of life (QoL) and psychological distress in a sample of 3,745 cancer patients across all tumor entities. In total, 37.9% patients suffered from cancer-related pain and 56.1% suffered from non-specific pain. Younger, female, less educated and unemployed patients reported pain more frequently and more severe pain (p less then 0.001). Pain was associated with distress, depression, anxiety, QoL, tumor stage (p less then 0.001), and time since diagnosis (p = 0.012). Pain assessment and pain management should be a routine part of cancer treatment and cancer survivorship care plans.Spine pain is a highly prevalent condition affecting over 11% of the world’s population. It is the single leading cause of activity limitation and ranks fourth in years lost to disability globally, representing a significant personal, social, and economic burden. For the vast majority of patients with back and neck pain, a specific pathology cannot be identified as the cause for their pain, which is then labeled as non-specific. In a growing proportion of these cases, pain persists beyond 3 months and is referred to as chronic primary back or neck pain. To decrease the global burden of spine pain, current data suggest that a conservative approach may be preferable. One of the conservative management options available is spinal manipulative therapy (SMT), the main intervention used by chiropractors and other manual therapists. The aim of this narrative review is to highlight the most relevant and up-to-date evidence on the effectiveness (as it compares to other interventions in more pragmatic settings) and effthat predict these effects remain to be determined to target patients who are more likely to obtain positive outcomes from SMT.Introduction Transcutaneous electrical nerve stimulation (TENS) for migraine involves the application of pulsatile stimulation through electrodes placed on the forehead to target the underlying trigeminal nerves. It is a simple, safe modality and has secured clinical approval in several markets including the European Union and the United States. Despite nearing almost 7 years of use (postclinical approval), the exact mechanism of action is not fully known. Guided by the need to stimulate the trigeminal nerves bilaterally, electrode dimensions are simply required to extend enough to cover the underlying nerves. The goal of this study is to examine induced current flow [magnitude and spatial distribution of electric field (EF)] and another driver of stimulation [activating function (AF)] due to TENS therapy for migraine for the first time. We further consider the effect of changing the electrode dimension and shape and propose a design modification to deliver optimal flow. Methods We developed the first ultra-h stimulation was further apparent. Given the existing electrode design’s established efficacy, our results imply that preferential targeting of the ST nerve is related to the mechanism of action. Additionally, if comparable targeting of all three nerves continues to hold promise, the extended V-shaped +CS montage presents an optimized configuration to explore in clinical studies.This brief report details a pilot analysis conducted to explore racial differences in pain sensitivity and unpleasantness between cognitively healthy Black and White adults, stratified by sex. A total of 24 cognitively healthy adults (12 Black and 12 White) from two completed studies were matched by age and sex, and divided into two groups based on race. Stratified analyses by sex demonstrated that Black females reported experiencing pain intensity ratings of all three intensity sensations at lower temperatures than White females. These findings will inform future research studies to determine if these results hold true in a fully-powered sample and should include mixed methodologies, incorporating neuroimaging data to further assess this phenomenon. Improving pain assessment and management across racial/ethnic groups will help healthcare providers such as nurses and physicians to ensure optimal quality of life for all.