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Fibromyalgia (FM) is a chronic noncommunicable disorder characterized by a constellation of symptoms that include fatigue, depression and chronic pain. FM affects 2%-8% of the U.S. population, 2% of the global population, with 61%-90% of FM diagnoses attributed to women. Key causal factors leading to the development and severity of FM-related symptoms have not yet been identified. The purpose of this article is to report relationships among identified metabolites and levels of fatigue, depression, pain severity, and pain interference in a sample of 20 women with FM. In this secondary analysis, we conducted global metabolomic analysis and examined the data for relationships of metabolite levels with self-reported symptoms of fatigue, depression, pain severity, and pain interference. Results revealed six metabolites (6-deoxy-hexose; pantothenic acid; ergothioneine; l-carnitine; n-acetylserotonin; butyrobetaine) and their associated metabolic pathways such as carnitine synthesis, lipid oxidation, tryptophan metabolism, beta-alanine metabolism and pantothenic and Coenzyme-A biosynthesis that were either positively or inversely related to pain severity, pain interference, or both. The preliminary data presented suggest that metabolites representing energy, amino acid, or lipid classification may be associated with pain symptom severity and interference in women with FM. Future work will confirm these findings in a large, comparative cohort, targeting metabolites and metabolite pathways to better understand the relationships of metabolites and symptomology.
Learn More >Neuropathic pain is a common symptom of multiple sclerosis (MS) and current treatment options are ineffective. In this study, we investigated whether endoplasmic reticulum (ER) stress in dorsal root ganglia (DRG) contributes to pain hypersensitivity in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Inflammatory cells and increased levels of ER stress markers are evident in post-mortem DRGs from MS patients. Similarly, we observed ER stress in the DRG of mice with EAE and relieving ER stress with a chemical chaperone, 4-phenylbutyric acid (4-PBA), reduced pain hypersensitivity. In vitro, 4-PBA and the selective PERK inhibitor, AMG44, normalize cytosolic Ca transients in putative DRG nociceptors. We went on to assess disease-mediated changes in the functional properties of Ca -sensitive BK-type K channels in DRG neurons. We found that the conductance-voltage (GV) relationship of BK channels was shifted to a more positive voltage, together with a more depolarized resting membrane potential in EAE cells. Our results suggest that ER stress in sensory neurons of MS patients and mice with EAE is a source of pain and that ER stress modulators can effectively counteract this phenotype.
Learn More >There is often dissociation between inflammatory activity and abdominal pain in children with inflammatory bowel disease (IBD), suggesting other factors may play a role in the pain experience.
Learn More >This study evaluated theoretically derived mechanisms and common therapeutic factors to test their role in accounting for pain-related outcome change during group-delivered cognitive therapy (CT), mindfulness meditation (MM) and mindfulness-based cognitive therapy (MBCT) for chronic low back pain.
Learn More >This study assessed the utility of the Multidimensional Patient Impression of Change (MPIC) questionnaire in a pediatric pain population following interdisciplinary treatment.
Learn More >Prevention of headaches via avoidance of triggers remains the main behavioral treatment suggestion for headache management despite trigger avoidance resulting in increases in potency, lifestyle restrictions, internal locus of control decreases, pain exacerbation and maintenance. New approaches, such as Acceptance and Commitment Therapy (ACT), instead emphasize acceptance and valued living as alternatives to avoidance. Though ACT is an empirically supported treatment for chronic pain, there is limited evidence for headache management whilst preliminary outcome studies are afflicted with methodological limitations. This study compared an ACT-based group headache-specific intervention to wait-list control, in a randomized clinical trial, on disability, distress, medical utilization, functioning and quality of life. 94 individuals with primary headache (84% women; Mage=43 years; 87.35% migraine diagnosis) were randomized into two groups (47 in each). Assessments occurred: before, immediately after, and at 3-months following treatment end. Only the ACT group was additionally assessed at 6- and 12-months follow-up. Results (intent to treat analyses corroborated by linear-mixed-model analyses) showed substantial improvements in favor of ACT compared to control, on disability, quality of life, functional status, and depression at 3-, 6-, and 12-month follow-up. Improvements were maintained in the ACT group at 6- and 12-month follow-up. At 3-month follow-up, clinical improvement occurred in headache-related disability (63%) and 65% in quality of life in ACT vs. 37% & 35% in control. These findings offer new evidence for the utility and efficacy of ACT in localized pain conditions and yields evidence for both statistical and clinical improvements over a years' period. Perspective: An Acceptance and Commitment Therapy approach focusing on acceptance and values-based activities, was found to improve disability, functioning and quality of life among patients with primary headaches. Trial registration: Clinical trials.gov registry (NCT02734992).
Learn More >The measurement of pain in animals is surprisingly complex, and remains a critical issue in veterinary care and biomedical research. Based on the known utility of pain measurement via facial expression in verbal and especially non-verbal human populations, "grimace scales" were first developed a decade ago for use in rodents and now exist for 10 different mammalian species. This review details the background context, historical development, features (including duration), psychometric properties, modulatory factors, and impact of animal grimace scales for pain.
Learn More >To determine whether training with a brain-computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain.
Learn More >Although convincing experimental evidence indicates that Na/K/Cl cotransporter 1 (NKCC1) is involved in spinal nociceptive information processing and in the generation of hyperalgesia and allodynia in chronic pain states, the cellular distribution of NKCC1 in the superficial spinal dorsal horn is still poorly understood. Because this important piece of knowledge is missing, the effect of NKCC1 on pain processing is still open to conflicting interpretations. In this study, to provide the missing experimental data, we investigated the cellular distribution of NKCC1 in the superficial spinal dorsal horn by immunohistochemical methods. We demonstrated for the first time that almost all spinal axon terminals of peptidergic nociceptive primary afferents express NKCC1. In contrast, virtually all spinal axon terminals of nonpeptidergic nociceptive primary afferents were negative for NKCC1. Data on the colocalization of NKCC1 with axonal and glial markers indicated that it is almost exclusively expressed by axon terminals and glial cells in laminae I-IIo. In lamina IIi, however, we observed a strong immunostaining for NKCC1 also in the dendrites and cell bodies of PV-containing inhibitory neurons and a weak staining in PKCγ-containing excitatory neurons. Our results facilitate further thinking about the role of NKCC1 in spinal pain processing.
Learn More >Osteoarthritis is a mechanical abnormality characterized by chronic joint pain associated with degeneration of the articular cartilage, synovitis, and local inflammation, leading to loss of function and pain. A connection exists between the peripheral nervous system and inflammatory joint degeneration. The process by which inflammation is influenced by the nervous system is known as neuroinflammation. One of the neuropeptides involved in peripheral neuroinflammation is nociceptin, a peptide related to the opioid class of substances. Nociceptin has both pro- and anti-inflammatory effects. Some studies show that nociceptin can be measured in synovial fluid, while other studies have not been able to detect it. The presence of nociceptin in synovial fluid could imply a molecular role for the neuropeptide in the joint, both physiologically as well as pathophysiologically. The goal of this pilot study was to determine whether nociceptin was present in the synovial fluid of osteoarthritic knees.
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