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We aimed to systematically assess the effectiveness and tolerability of erenumab in a clinical setting, specifically a tertiary headache center.
Learn More >Effective treatment of neuropathic pain is challenging as its underlying mechanism remains largely unknown. Recently, the participation of brain-derived neurotrophic factor (BDNF) in neuropathic pain has been attracting increased attention. BDNF binds to a member of the tyrosine kinase receptor family, the TrkB receptor, that is specific for BDNF and is the transmembrane receptor on the posterior horn of spinal cord. In the present study, we purified two proteins that included the BDNF-binding domain of TrkB (eTrkB) and eTrkB coupled with a liposomal outer surface (liposomal eTrkB) in order to inhibit the BDNF-TrkB pathway in neuropathic pain. Results of the pull-down assay showed that eTrkB was bound to BDNF. We investigated the neuropathic pain suppression effect of this purified protein by its intrathecal administration in a rat neuropathic pain model. Mechanical and thermal hyperalgesia induced by L5 lumbar nerve ligation was markedly suppressed by treatment with eTrkB protein. Furthermore, we showed a prolonged algetic inhibition by liposomal eTrkB protein treatment. In conclusion, this study suggests that eTrkB, which sequesters endogenous BDNF and inhibits the BDNF-TrkB pathway, may prove to be a novel analgesic to treat neuropathic pain.
Learn More >Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT receptor agonist approved in the United States for the acute treatment of migraine. In SPARTAN and SAMURAI (double-blind Phase 3 clinical trials), patients with migraine were randomized to oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Lasmiditan increased the proportion of pain-free and most bothersome symptom (MBS)-free patients at 2 hours after dose compared with placebo. Most common treatment-emergent adverse events (TEAEs) were dizziness, paraesthesia, somnolence, fatigue, nausea, muscular weakness, and hypoesthesia. Based upon literature review of common migraine comorbidities, Anxiety, Allergy, Bronchial, Cardiac, Depression, Fatigue, Gastrointestinal, Hormonal, Musculoskeletal/Pain, Neurological, Obesity, Sleep, and Vascular Comorbidity Groups were created. Using pooled results, efficacy and TEAEs were assessed to compare patients with or without a given common migraine comorbidity. To compare treatment groups, p-values were calculated for treatment-by-subgroup interaction, based on logistic regression with treatment-by-comorbidity condition status (Yes/No) as the interaction term; study, treatment group, and comorbidity condition status (Yes/No) were covariates. Differential treatment effect based upon comorbidity status was also examined. Trial registration at clinicaltrials.gov: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Across all the Comorbidity Groups, with the potential exception of fatigue, treatment-by-subgroup interaction analyses did not provide evidence of a lasmiditan-driven lasmiditan versus placebo differential treatment effect dependent on Yes versus No comorbidity subgroup for either efficacy or TEAE assessments. The efficacy and safety of lasmiditan for treatment of individual migraine attacks appear to be independent of comorbid conditions.
Learn More >Osteoarthritis results in chronic pain and loss of function. Proinflammatory cytokines create both osteoarthritis pathology and pain. Current treatments are poorly effective, have significant side effects, and have not targeted the cytokines central to osteoarthritis development and maintenance. Interleukin-10 is an anti-inflammatory cytokine that potently and broadly suppresses proinflammatory cytokine activity. However, interleukin-10 protein has a short half-life in vivo and poor joint permeability. For sustained IL-10 activity, we developed a plasmid DNA-based therapy that expresses a long-acting human interleukin-10 variant (hIL-10var). Here, we describe the 6-month GLP toxicology study of this therapy. Intra-articular injections of hIL-10var pDNA into canine stifle joints up to 1.5 mg bilaterally were well-tolerated and without pathologic findings. This represents the first long-term toxicologic assessment of intra-articular pDNA therapy. We also report results of a small double-blind, placebo-controlled study of the effect of intra-articular hIL-10var pDNA on pain measures in companion (pet) dogs with naturally occurring osteoarthritis. This human IL-10-based targeted therapy reduced pain measures in the dogs, based on veterinary and owner ratings, without any adverse findings. These results with hIL-10var pDNA therapy, well-tolerated and without toxicologic effects, establish the basis for clinical trials of a new class of safe and effective therapies for OA.
Learn More >We intended to clarify the effect of gender and A118G polymorphism of Opioid Receptor μ1 (OPRM1) on the required morphine for patients to maintain Visual Analogue Scale ≦ 3 for post-operative pain control after total knee replacement (TKR).
Learn More >To compare medication use and health resource utilization between migraineurs with evidence of opioid use at emergency department visit versus no opioid use at emergency department visit, and to examine predictors of opioid use among migraineurs at emergency department visits.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is among the most disabling and frustrating problems for cancer survivors. The neurotoxicity caused by cisplatin varies greatly among patients, and few predictors of appearance, duration of symptoms, susceptibility, or severity are available. A deeper understanding of the mechanisms underlying individual differences in status, severity, or sensitivity in response to cisplatin treatment is therefore required. By analyzing the GSE64174 gene expression profile and constructing a weighted gene co-expression network analysis (WGCNA) network, we screened gene modules and hub genes related to CIPN status, severity and sensitivity. We first identified the transcriptome profile of mouse dorsal root ganglion (DRG) samples and transformed their genes to human DRG counterparts. We then constructed WGCNA gene modules via optimal soft-threshold power-identification and module-preservation analysis. Comprehensive analysis and identification of module hub genes were performed via functional-enrichment analysis and significant common hub genes were identified, including "Cytoscape_cytoHubba," "Cytoscape_MCODE," and "Metascape_MCODE." Brown, green, and blue modules were selected to represent CIPN sensitivity, status and severity, resepectively, via trait-module correlational analysis. Additionally, functional enrichment analysis results indicated that these three modules were associated with some crucial biological functions, such as neutrophil migration, chemokine-mediated signaling pathway, and PI3K-Akt signaling pathway. We then identified seven common hub genes via three methods, including CXCL10, CCL21, CCR2, CXCR4, TLR4, NPY1R, and GALR2, related to CIPN status, severity and sensitivity. Our results provide possible targets and mechanism insights into the development and progress of CIPN, which can guide further transformation and pre-clinical research.
Learn More >Concerns about adverse outcomes associated with opioid analgesic prescription have led to major guideline and policy changes. Substantial uncertainty remains, however, regarding the association between opioid prescription initiation and increased risk of subsequent substance-related morbidity.
Learn More >The opioid epidemic is a significant public health crisis in the United States, and chronic pain is a leading precipitating and maintaining factor for opioid misuse. To better understand substance misuse generally, research has examined motivational models of why people use substances, and pain management and affect-driven coping are cited as primary reasons for opioid misuse. Further, research examining psychosocial predictors of opioid misuse has identified anxiety sensitivity (AS; fear of anxiety-related physical sensations) as a unique predictor of opioid misuse severity, and it is possible that AS is uniquely related to opioid pain management and coping motives, which in turn, are related to opioid misuse. Therefore, the current study examined AS as a predictor of opioid pain management and coping motives, as well as the indirect effect of AS, through opioid motives, on opioid misuse status, among 292 adults (Mage = 45.76, SD = 11.20, 68.9% female) with chronic low back pain. Results for the current study support hypotheses that AS is significantly associated with pain management and coping motives (over and above variance of pain intensity) and indirectly associated with opioid misuse status through both motives. These results highlight the importance of better understanding opioid use motives in the context of chronic pain and provide potential treatment targets to add to a growing body of literature targeting psychosocial factors for opioid misuse. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Learn More >Epidemiological studies have shown that 6.9-10% of people suffer from neuropathic pain, a complex painful condition which is often undertreated. Data regarding the effectiveness of treatment options for patients with neuropathic pain is inconsistent, and there is no single treatment option that shows cost-effectiveness across studies.
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