Browse by Audience
To compare effectiveness of onabotulinumtoxinA and topiramate for chronic migraine (CM) prevention.
Learn More >The search for new ligands to treat neuropathic pain remains a challenge. Recently, oxytocin has emerged as an interesting molecule modulating nociception at central and peripheral levels, but no attempt has been made to evaluate the effect of recurrent oxytocin administration in neuropathic pain. Using male Wistar rats with spinal nerve ligation, we evaluated the effects of recurrent spinal (1 nmol; given by lumbar puncture) or peripheral (31 nmol; given by intraplantar injection in the ipsilateral paw to spinal nerve ligation) oxytocin administration on pain-like behavior in several nociceptive tests (tactile allodynia and thermal and mechanical hyperalgesia) on different days. Furthermore, we used an electrophysiological approach to analyze the effect of spinal 1 nmol oxytocin on the activity of spinal dorsal horn wide dynamic range cells. In neuropathic rats, spinal or peripheral oxytocin partially restored the nociceptive threshold measured with the von Frey filaments (tactile allodynia), Hargreaves (thermal hyperalgesia) and Randall-Selitto (mechanical hyperalgesia) tests for 12 days. These results agree with electrophysiological data showing that spinal oxytocin diminishes the neuronal firing of the WDR neurons evoked by peripheral stimulation. This effect was associated with a decline in the activity of primary afferent Aδ- and C-fibers. The above findings show that repeated spinal or peripheral oxytocin administration attenuates the pain-like behavior in a well-established model of neuropathic pain. This study provides a basis for addressing the therapeutic relevance of oxytocin in chronic pain conditions.
Learn More >This study evaluated suicidality and its risk factors in patients with tension-type headache (TTH). We recruited new patients with TTH who visited general hospitals. We recorded their clinical characteristics and conducted the Headache Impact Test-6 (HIT-6) and the Insomnia Severity Index (ISI) for assessment. We also interviewed the patients to identify major depressive disorder (MDD), generalized anxiety disorder (GAD), and suicidality with the Mini International Neuropsychiatric Interview-Plus Version 5.0.0 (MINI). The frequency of suicidality was compared between TTH patients and healthy controls. Major risk factors for suicidality were also determined. A total of 332 TTH patients with the same number of healthy controls were recruited from five general hospitals. Suicidality was observed in 82 (24.7%) TTH patients. The frequency of suicidality was significantly higher in patients with TTH than in the controls. Furthermore, the frequency of suicidality was higher in patients with chronic TTH (CTTH) than in the controls. The major risk factors for suicidality were MDD, GAD, a low education level, insomnia, chronicity of TTH, and pericranial tenderness. Suicidal ideation or attempt seems to be a common feature in TTH. Therefore, it is important to identify risk factors related to suicidality in TTH patients, which may help reduce suicidality.
Learn More >Our knowledge of central sensitization (CS) in chronic low back pain (CLBP) is limited. 2011 fibromyalgia criteria and severity scales (2011 FM survey) has been used to determine FM positive as a surrogate of CS. The major features of CS including widespread hyperalgesia and dysfunction of the descending inhibitory pathways can be identified by pressure pain threshold (PPT) and conditioned pain modulation (CPM) tests. The purpose of the study was to examine neurophysiological characteristics and psychosocial symptoms in a subgroup of FM positive CLBP compared to FM negative CLBP patients.
Learn More >Uremic pruritus with elevated levels of calcium phosphate (CaP) in skin is a common symptom in patients with chronic kidney disease (CKD). In this study, we demonstrate that intradermal injection of CaP into mice-triggered scratching by up-regulating the IL-6 in skin and phosphorylation of ERKs in dorsal root ganglion (DRG) in a dose-dependent manner. IL-6 is essential because the CaP-induced up-regulation of phosphorylated (p)-ERK in DRG was considerably reduced in the IL-6 knockout mice. Microarray analysis in conjunction with real-time PCR revealed a higher mRNA expression of Bruton's tyrosine kinase (BTK) gene in DRG after CaP injection. The inhibition of BTK by ibrutinib noticeably diminish the CaP-induced up-regulation of IL-6 and p-ERK in mice. A high amount of IL-6 was detected in itchy skin and blood of patients with CKD. The expressions of p-BTK and p-ERK in DRG primary cells reached maximum levels at 1 and 10 min, respectively, after treatment of recombinant IL-6 and were significantly reduced by treatment of IL-6 along with ibrutinib. The mechanism by which the CaP-induced pruritus mediated by the IL-6/p-BTK/p-ERK signaling was revealed.-Keshari, S., Sipayung, A. D., Hsieh, C.-C., Su, L.-J., Chiang, Y.-R., Chang, H.-C., Yang, W.-C., Chuang, T.-H., Chen, C.-L., Huang, C.-M. The IL-6/p-BTK/p-ERK signaling mediates the calcium phosphate-induced pruritus.
Learn More >The marked increase in deaths related to opioid drugs since 1999 was associated with an increase in the number of prescriptions for opioid drugs. This was accompanied by increasing demand for improved management of chronically painful conditions. These factors suggest that improvements are needed in the education of physicians with regard to the management of chronic pain, the optimal therapeutic application of opioid drugs, and the avoidance of substance use disorders. In this paper we address the evidence that physician education can influence prescribing practices and discuss approaches to enhancing the pre-clinical and clinical education of medical students in pain management and substance use disorders. SIGNIFICANCE STATEMENT: N/A.
Learn More >Patients qualifying for Medicare disability have the highest rates of opioid use compared with older Medicare beneficiaries and commercial insurance beneficiaries. Research on opioid overdose deaths in this population can help identify appropriate interventions.
Learn More >Individuals with chronic pain commonly report significant functional impairment and reduced quality of life. Despite this, little is known about psychological processes and mechanisms underpinning enhancements in well-being within this population. The study aimed to investigate whether (1) increased levels of pain intensity and interference were associated with lower levels of mental well-being, (2) increased positive goal engagement was associated with higher levels of mental well-being and (3) whether the relationships between pain characteristics and mental well-being were mediated by increased positive goal engagement. A total of 586 individuals with chronic pain participated in the cross-sectional, online study. Participants completed self-report measures to assess pain intensity and interference, mental well-being and goal motivation variables. Results showed that pain interference and positive goal engagement were associated with mental well-being. Moreover, the relationship between pain interference and mental well-being was partially mediated by positive goal engagement. The results provide tentative evidence for the protective role of positive goal engagement in enabling individuals with chronic pain to maintain a sense of mental well-being. The study develops the biopsychosocial model of chronic pain by examining the roles and relationships of relevant yet previously unexplored psychological constructs. The promotion of mental well-being through the enhancement of positive goal engagement is discussed, offering a platform for further research and clinical interventions.
Learn More >Chronic pain is one of the commonest reasons individuals seek medical attention. It is a major issue because of the wide inter-individual variability in the analgesic response. This might be partly explained by the presence of variants in genes encoding molecules involved in pharmacodynamics and pharmacokinetics. The aim was to analyze opioid effectiveness in chronic low-back pain (CLBP) relief after opioid titration, unveiling the impact of pharmacogenetics.
Learn More >The role of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) in atopic dermatitis (AD) is unknown. This study is envisioned to lead to the previously unreported SNARE function in AD-related cytokine secretion and epidermis-nerve communication. Herein, we report that various cytokines were simultaneously upregulated and co-released in the innate immunity-activated primary human keratinocytes (phKCs). AD-related cytokines thymic stromal lymphopoietin (TSLP), endothelin-1 (ET-1) or inflammatory TNF-α activated distinct but overlapping sensory neurons. Interestingly, TNF-α potentiated TSLP-induced Ca-influx, whereas ET-1 caused itch-selective B-type natriuretic peptide (BNP) release. In phKCs, BNP upregulated genes promoting dermatological and neuroinflammatory diseases and conditions. VAMP3, SNAP-29 and syntaxin4 proved important in driving cytokine release from phKCs. Depletion of VAMP3 inhibited nearly all the cytokine release including TSLP and ET-1. Accordingly, VAMP3 co-occurred with ET-1 in AD patient skin. Our study pinpoints the pivotal role of SNAREs in mediating cytokine secretion related to AD. VAMP3 is identified as a suitable target for developing broad-spectrum anti-cytokine therapeutics for controlling itch and atopic skin inflammation.
Learn More >