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Sub-anesthetic ketamine is frequently used as an analgesic to reduce perioperative opioid consumption and has also been shown to have antidepressant effects. Side effects of ketamine include dizziness, diplopia, nystagmus, and psychomimetic effects. It is unclear what clinical factors may be associated with ketamine-related adverse drug events (ADEs).
Learn More >Current treatment options for chronic pain and depression are largely medication-based, which may cause adverse side effects. Integrative Medical Group Visits (IMGV) combines mindfulness techniques, evidence based integrative medicine, and medical group visits, and is a promising adjunct to medications, especially for diverse underserved patients who have limited access to non-pharmacological therapies.
Learn More >The Internet in general, and YouTube in particular, is now one of the most popular sources of health-related information. Pain neuroscience education has become a primary tool for managing persistent pain, based in part on the discovery that information about pain can change pain. Our objective was to examine the availability, characteristics, and content of YouTube videos that address the neuroscience of pain.
Learn More >Exercise is known to be an important component of treatment programs for individuals with neck pain. The study aimed to compare the effects of semispinalis cervicis (extensor) training, deep cervical flexor (flexor) training, and usual care (control) on functional disability, pain intensity, craniovertebral (CV) angle, and neck-muscle strength in chronic mechanical neck pain.
Learn More >A number of studies have been published proposing various approaches to the treatment of neuropathic pain; however, to our knowledge, no attempts have been made to compare gabapentin and fentanyl in patients with lumbar radiculopathy. We evaluated the relative efficacy and safety of fentanyl matrix and gabapentin for the treatment of chronic neuropathic pain of radicular origin. The study was designed as a randomized blind multicentered parallel-group noninferiority trial. A total of 108 patients with moderate-to-severe pain (≥4 intensity on an 11-point numeric rating scale) were randomly prescribed either fentanyl matrix or gabapentin over a period of 56 days. In the primary analysis, the noninferiority of fentanyl matrix treatment was evaluated in relation to the efficacy of gabapentin based on the pain intensity difference (PID) at 56 days after the first dose of the drugs. Secondary endpoints included pain relief, improvement in functional status (the Korean-Oswestry Disability Index (K-ODI)), improvement in depressive symptoms (Korean-Beck Depression Index (K-BDI)) between the 28th and 56th day, and adverse events (AEs). Analysis of the primary efficacy endpoint established the noninferiority of fentanyl matrix compared with gabapentin, with no statistically significant difference observed in the PID after 56 days for the two treatment groups. Similarly, analysis of pain relief revealed no significant differences between the groups on days 28 and 56. There was no difference in the K-ODI and K-BDI between the groups during the study period. The overall incidence of at least one AE was similar for fentanyl matrix (67.3%) and gabapentin (69.6%). The most commonly reported AEs for patients treated with fentanyl matrix and gabapentin included dizziness (30.8% vs. 44.6%, respectively), somnolence (26.9% vs. 35.7%), and constipation (15.4% vs. 17.9%). This study demonstrated that the analgesic effect of fentanyl matrix is noninferior in comparison with gabapentin and supports the use of fentanyl matrix as an effective and safe treatment for moderate-to-severe chronic neuropathic pain. This trial is registered with NCT01127100.
Learn More >Type-A γ-aminobutyric (GABA) receptors are ligand-gated chloride channels with a very rich pharmacology. Some of their modulators, including benzodiazepines and general anaesthetics, are among the most successful drugs in clinical use and are common substances of abuse. Without reliable structural data, the mechanistic basis for the pharmacological modulation of GABA receptors remains largely unknown. Here we report several high-resolution cryo-electron microscopy structures in which the full-length human α1β3γ2L GABA receptor in lipid nanodiscs is bound to the channel-blocker picrotoxin, the competitive antagonist bicuculline, the agonist GABA (γ-aminobutyric acid), and the classical benzodiazepines alprazolam and diazepam. We describe the binding modes and mechanistic effects of these ligands, the closed and desensitized states of the GABA receptor gating cycle, and the basis for allosteric coupling between the extracellular, agonist-binding region and the transmembrane, pore-forming region. This work provides a structural framework in which to integrate previous physiology and pharmacology research and a rational basis for the development of GABA receptor modulators.
Learn More >Chronic widespread pain (CWP) is one of the most difficult pain conditions to treat due to an unknown etiology and a lack of innovative treatment design and effectiveness. Based upon preliminary findings within the fields of motivational psychology, integrative neuroscience, diaphragmatic breathing, and vagal nerve stimulation, we propose a new treatment intervention, motivational non-directive (ND) resonance breathing, as a means of reducing pain and suffering in patients with CWP. Motivational ND resonance breathing provides patients with a noninvasive means of potentially modulating five psychophysiological mechanisms imperative for endogenously treating pain and increasing overall quality of life.
Learn More >In 2016, a special interest group from the International Forum for the Study of Itch defined sensitive skin (SS) as a syndrome that manifests with the occurrence of unpleasant sensations (stinging, burning, pain, pruritus, and tingling sensations) after stimuli that should not cause a reaction, such as water, cold, heat, or other physical and/or chemical factors. The pathophysiology of sensitive skin is still poorly understood, but the symptoms described suggest inflammation and peripheral innervation. Only two publications have focused on sensitive skin transcriptomics. In the first study, the authors performed a microarray comparison of SS and non-sensitive skin (NSS) samples and showed differences in the expression of numerous genes in SS and NSS samples. Moreover, in the SS samples, two clusters of genes were identified, including upregulated and downregulated genes, compared to NSS samples. These results provide some interesting clues for the understanding of the pathophysiology of SS. The second study compared SS and NSS samples using RNA-seq assays. This method allowed the identification of long non-coding RNAs (lncRNAs) and differentially expressed mRNAs and provided a comprehensive profile in subjects with SS. The results showed that a wide range of genes may be involved in the pathogenesis of SS and suggested pathways that could be associated with them. In this paper, we discuss these two studies in detail and show how transcriptomic studies can help understand the pathophysiology of sensitive skin. We call for new transcriptomic studies on larger populations to be conducted before putative pathogenic mechanisms can be detected and analyzed to achieve a better understanding of this complex condition.
Learn More >Metacognitions, which are beliefs about our own thinking processes, can modulate worry and rumination and thereby influence emotional distress. This study aimed to develop a self-report measure of unhelpful pain-related metacognitions which might serve as a clinical and research tool to better understand pain catastrophizing, a significant risk factor for adverse pain outcomes. Two phases of validation are presented. Phase 1 reports on how the Pain Metacognitions Questionnaire (PMQ) was empirically developed through a qualitative study of 20 people with chronic back ( = 15) or knee ( = 5) pain in secondary or tertiary care and then validated in a large internet sample of people experiencing pain ( = 864). Rasch analysis yielded a 21-item scale with two dimensions (positive and negative metacognition) assessing how useful and problematic people believe rumination about pain to be, respectively. In Phase 2, further validation using a new sample ( = 510) replicated initial findings. Both PMQ subscales have good retest reliability ( = 0.76, = 0.72) and internal consistency (0.86, 0.87). They correlate negatively with mindfulness and positively with pain intensity, disability, anxiety, depression, catastrophizing, rumination, and metacognition. The PMQ also predicts unique variance in catastrophizing when other variables are controlled and predicts 'patient' status for pain catastrophizing. Sensitivity analysis yielded preliminary suggestions for clinically meaningful cut-offs. Unhelpful pain metacognitions can be validly and reliably measured using a self-report instrument. Future studies using the PMQ might shed new light on pain-related thinking processes to develop better interventions for people prone to worry and rumination about their pain.
Learn More >Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder.
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