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Neuropathic pain research has grown impressively in the past two decades, as evidenced by improvements in research quality and increments in the number of research papers. In views of this situation, the use of quantitative measurements to analyze and characterize existing research has become imperative. The aim of this research is to identify and analyze the 100 most-cited papers in neuropathic pain research. Neuropathic pain-related articles published between 2000 and 2020 were screened from Web of Science (WOS) by using the following subject terms: TI = (Neuralgia$ OR Neurodynia$ OR "Neuropathic pain" OR sciatica OR "Nerve pain$"). The publications were ranked in a descending order on the basis of citation counts, and the top 100 most-cited neuropathic pain papers were determined. Subsequently, we conducted a bibliometric study to determine the authors, journals, countries, and institutions that contributed the most to the top 100 neuropathic pain lists; describe the keywords and hotspots of the top 100 most-cited papers; and explore the factors associated with successful citations. The top 100 most-cited papers were published from 2000 to 2017, and 2003 had the largest number of published papers ( = 16). The mean number of citations per paper was 480.72, with a range of 262-1,569. Forty-four kinds of journals contributed to the top 100 most-cited papers, which were predominantly published in "Pain" ( = 23). The USA was determined to be the leader of neuropathic pain research in terms of quality and quantity. This study provides a comprehensive list of the most influential papers on neuropathic pain and demonstrates the important advances in this field to help understand academic concerns and the directions of technological innovations in neuropathic pain worldwide.
Learn More >Itch draws our attention to allow imposing action against bodily harm (e.g., remove insects). At the same time, itch is found to interfere with ongoing tasks and daily life goals. Despite the key role of attention in itch processing, interventions that train individuals to automatically disengage attention from itch cues are lacking. The present proof-of-principle attention bias modification (ABM) training study was aimed at investigating whether attention to itch as well as sensitivity to mild itch can be changed. Healthy volunteers were randomized over three ABM-training conditions. Training was done via a modified pictorial dot-probe task. In particular, participants were trained to look away from itch stimuli ( = 38), toward itch stimuli ( = 40) or not trained toward or away from itch at all (sham training, = 38). The effects of the ABM-training were tested primarily on attention to itch pictures. Secondarily, it was investigated whether training effects generalized to alterations in attention to itch words and mechanical itch sensitivity. The ABM-training did not alter attention toward the itch pictures, and there was no moderation by baseline levels of attention bias for itch. Also, attention bias to the itch words and itch sensitivity were not affected by the ABM-training. This study was a first step toward trainings to change attention toward itch. Further research is warranted to optimize ABM-training methodology, for example increasing motivation of participants. Eventually, an optimized training could be used in patient populations who suffer most from distraction by their symptoms of itch. Identifier: NL6134 (NTR6273). The website URL is: https://www.trialregister.nl/.
Learn More >Nerve growth factor (NGF) belongs to the neurotrophin family and plays a fundamental role in the endurance of sensory and sympathetic neurons during embryogenesis. NGF, by interacting with tropomyosin receptor kinase A receptor (TrkA), modulates the pain pathway through the enhancement of the neurotrophic and nociceptor functions. Moreover, it has been demonstrated that NGF is upregulated in patients with chronic pain syndromes, which are difficult to treat. Thus, new non-pharmacological approaches, based on the use of different species-specific monoclonal antibodies (mAbs) targeting the NGF pathway, have been tested for the treatment of chronic pain in preclinical and clinical studies. With regard to preclinical investigations, anti-NGF mAbs have been used for the management of osteoarthritis (OA) and chronic low back pain animal models, with encouraging results. Moreover, anti-NGF mAb therapy is effective in animal models of neuropathic cancer pain. As regards patients with OA, although phase II and phase III clinical trials with tanezumab led to pain reduction, the safety was not observed in all these patients. Here, we review the preclinical and clinical studies on anti-NGF mAb therapy in chronic syndromes, dissect the role of NGF in pain transduction, and highlight the use of anti-NGF mAbs in humans.
Learn More >Calcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (K ) channels. Here, we investigated the effect of the K channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.
Learn More >The aim of this article is to describe the consensus process used to develop an acupuncture intervention protocol for an NIH-funded pragmatic randomized controlled trial (PRCT) of acupuncture for the management of chronic low back (cLBP) in older adults (BackInAction).
Learn More >The transient receptor potential vanilloid-superfamily member 3 (TRPV3) channel is implicated in a variety of physiological processes, including temperature sensing, nociception and itch, maintenance of the skin barrier, wound healing, hair growth, and embryonic development. TRPV3 is also associated with various skin diseases, including Olmsted syndrome, atopic dermatitis, and rosacea. Studies of TRPV3 are of fundamental importance for structural pharmacology aimed at the design of drugs targeting this channel and for understanding the molecular basis of temperature sensing. Here we describe a detailed protocol for expression and purification of chemically pure and stable TRPV3 protein that is suitable for structural and functional characterization of this channel, in particular for cryo-EM sample preparation and high-resolution 3D reconstruction.
Learn More >The inconsistent use of standardized approaches for classifying postamputation pain (PAP) has been a barrier to establishing its prevalence.
Learn More >Cannabis products have become easily available and accessible after decriminalization of cannabis for recreational and medicinal use in many states. Cannabidiol (CBD) has been of increasing interest to patients and is being used to self-medicate a variety of ailments. However, very limited information is available to patients and providers to form an educated opinion regarding its indicated use to treat the many conditions this substance has been implied to be helpful for. The aim of this survey was to learn about participants' attitudes and views towards cannabis-based medicine (CBM) with a focus on perception of "CBD" and its potential role for pain management.
Learn More >Chronic pruritus affects up to 70% of patients with immune-mediated hepatobiliary disorders. Antagonists of the μ-opioid receptor (MOR) and agonists of the κ-opioid receptor (KOR) are used to treat hepatic itch, albeit with limited success. An imbalance between ligands of MOR and KOR receptors has recently been suggested as a potential mechanism of hepatic pruritus. In this study, we therefore investigated systemic levels of important endogenous opioids such as β-endorphin, dynorphin A, Leu- and Met-enkephalin in plasma of a large cohort of well-characterized patients with immune-mediated cholestatic disorders, including patients with liver cirrhosis, and during effective anti-pruritic therapy. Plasma samples and clinical data were prospectively collected from well-characterized patients with primary/secondary sclerosing cholangitis (PSC/SSC), primary biliary cholangitis (PBC) and overlap syndromes suffering from pruritus ( = 29) and age-, gender- and disease-matched controls without pruritus ( = 27) as well as healthy controls ( = 20). General laboratory testing for hepatobiliary and renal function was performed. Levels of β-endorphin, dynorphin A, Leu- and Met-enkephalin were quantified in plasma by ELISA. Intensity of pruritus over the last week was evaluated using a visual analog scale (VAS, 0-10). PBC and PSC patients with or without pruritus did neither differ in disease entity, disease stage, nor in the presence of cirrhosis. While both dynorphin A and β-endorphin concentrations were lower in pruritic patients compared to those without pruritus and healthy controls, the MOR/KOR ligand ratio was unaltered. No significant differences were observed for Leu- and Met-enkephalin concentrations. Opioid levels correlated with neither itch intensity nor stage of disease. Cirrhotic patients displayed higher concentrations of MOR agonist Leu-enkephalin and KOR agonist dynorphin A. Endogenous opioid levels remained largely unchanged after successful treatment with the potent anti-pruritic drugs rifampicin and bezafibrate. Endogenous opioid levels and the MOR/KOR ligand ratio neither correlate with itch intensity nor differentiate pruritic from non-pruritic patients with immune-mediated liver diseases. Thus, endogenous opioids may modulate signaling pathways involved in hepatic pruritus, but are unlikely to represent the major pruritogens in liver disease.
Learn More >New therapeutic alternatives for pain relief include the use of phosphodiesterase-5 (PDE5) inhibitors, which could prevent the transmission of painful stimuli by neuron hyperpolarization via nitric oxide (NO)/cyclic 3',5'-guanosine monophosphate (cGMP) pathway. The present work investigated the antinociceptive activity of a new PDE5 inhibitor, lodenafil carbonate, in inflammatory and neuropathic pain models.
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