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RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities.
Learn More >Exposure (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.
Learn More >The sensitizing effect of capsaicin has been previously characterized using laser and contact heat evoked potentials (LEPs and CHEPs) by stimulating in the primary area of hyperalgesia. Interestingly, only CHEPs reveal changes consistent with notion of peripheral sensitization (i.e., reduced latencies). The aim of this study was to investigate contact heat stimulation parameters necessary to detect peripheral sensitization related to the topical application of capsaicin, and therefore significantly improve the current method of measuring peripheral sensitization via CHEPs. Rapid contact heat stimulation (70°C/s) was applied from three different baseline temperatures (35, 38.5, and 42°C) to a 52°C peak temperature, before and after the topical application of capsaicin on the hand dorsum. Increased pain ratings in the primary area of hyperalgesia were accompanied by reduced N2 latency. Changes in N2 latency were, however, only significant following stimulation from 35 and 38.5°C baseline temperatures. These findings suggest that earlier recruitment of capsaicin-sensitized afferents occurs between 35 and 42°C, as stimulations from 42°C baseline were unchanged by capsaicin. This is in line with reduced thresholds of type II A-delta mechanoheat (AMH) nociceptors following sensitization. Conventional CHEP stimulation, with a baseline temperature below 42°C, is well suited to objectively detect evidence of peripheral sensitization.
Learn More >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.
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