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The multi-functional neuropeptide calcitonin gene-related peptide (CGRP) plays a major role in the pathophysiology of migraine. The detection of elevated CGRP levels during acute migraine headache was the first evidence of the importance of the peptide. Since then, elevated CGRP levels have been detected not only during spontaneous and experimentally induced migraine attacks but also interictally. However, the detection of CGRP in peripheral blood shows conflicting results. In this respect, alternative detection methods are needed and have been already proposed. This article summarizes what we have learned from studies investigating CGRP in jugular and peripheral blood and reviews the latest state of research concerning the detection of CGRP in saliva and tear fluid as well as their contribution to our understanding of migraine pathophysiology.
Learn More >Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1β, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.
Learn More >Chronic orofacial pain is prevalent and debilitating. Psychological and social factors place a heavy burden on this population but are often overlooked. Here, we offer the first comprehensive qualitative conceptualization of the challenges of living with chronic orofacial pain through a biopsychosocial perspective to inform multifaceted care for this population.
Learn More >Primary headache is a very common and disabling disease. The burden of pain and recurrent attacks may lead to a poor quality of life, anxiety and depression. An increased risk of low functioning and curricular performances in young patients with primary headache has been described. The mechanisms underlying the relationship between migraine and poor school achievement may be various and could be a reflection of weak cognitive skills. Data concerning the cognitive functioning in the free pain interval in pediatric age are under-investigated and results are far from conclusive. The present review article suggests that, though considered a benign disease, pediatric migraine may be associated to altered neuropsychological functioning in the interictal phase. Although children and adolescents with migraine generally have a normal intelligence, they may show a not homogeneous cognitive profile, characterized by possible difficulties in verbal skills, in particular comprehension abilities. Pediatric primary headache may present altered neuropsychological functioning involving attentional resources, processing speed and memory, particularly verbal memory. Given the impact that this disease can have on school performance and the tendency to persist from childhood to adulthood, a cognitive screening in young patients affected by primary headache is pivotal. Additional neuropsychological research using more homogenous methods is needed.
Learn More >Although activation of microglial cells is critical in developing brain disorders, their role in anxiety-like behaviors in pain is still vague. This study indicates that alteration of microglia's neuronal spine engulfment capacity in ventral zona incerta (ZI ) leads to significant pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud's Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZI (ZI ) in brain slices, we observed decreased activity in ZIv and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZI of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZI significantly relieved pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZI induced pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZI and increased microglial engulfment of spines in ZI of CFA1D mice. Furthermore, pain sensitization and anxiety-like behaviors were reversed when the ZI of CFA1D-treated mice were chemically inhibited by intra-ZI minocycline injection, accompanied by the recovery of decreased ZI excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZI , thus promoting the development of anxiety-like behaviors in acute pain.
Learn More >Neuropathic pain (NP), caused by an injury or a disease affecting the somatosensory nervous system of the central and peripheral nervous systems, has become a global health concern. Recent studies have demonstrated that epigenetic mechanisms are among those that underlie NP; thus, elucidating the molecular mechanism of DNA methylation is crucial to discovering new therapeutic methods for NP. In this review, we first briefly discuss DNA methylation, demethylation, and the associated key enzymes, such as methylases and demethylases. We then discuss the relationship between NP and DNA methylation, focusing on DNA methyltransferases including methyl-CpG-binding domain (MBD) family proteins and ten-eleven translocation (TET) enzymes. Based on experimental results of neuralgia in animal models, the mechanism of DNA methylation-related neuralgia is summarized, and useful targets for early drug intervention in NP are discussed.
Learn More >Guselkumab safety and efficacy profiles in psoriasis have been showed by VOYAGE (1 and 2) trials. Although trial results have been already previously confirmed by real-life studies, long-term real-life data, and drug survival data about guselkumab are still poor.
Learn More >Transcranial magnetic stimulation, as a relatively new type of treatment, is a safe and non-invasive method for pain therapy. Here, we used CiteSpace software to visually analyze 440 studies concerning transcranial magnetic stimulation in pain research from 2010 to 2021, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the process of discovery in this field. The United States ranked first in this field. Lefaucheur JP, Fregni F, and Andrade ACD made great contributions to this field of study. The most prolific institution was University of São Paulo. The four main hot keywords were neuropathic pain, motor cortex, connectivity, and non-invasive brain stimulation. There were three main points that were generally accepted: (1) definite analgesic effect of high-frequency rTMS of M1 contralateral to pain side in neuropathic pain; (2) there are inconclusive recommendations regarding rTMS of the dorsolateral prefrontal cortex (DLPFC) in fibromyalgia and neuropathic pain; (3) there is low-quality evidence that single doses of high-frequency rTMS of the motor cortex may have short-term effects on chronic pain. This bibliometric analysis indicated that prospective, multi-center, large-sample, randomized controlled trials are still needed to further verify the effectiveness of various transcranial magnetic stimulation parameters in pain research.
Learn More >This study sought to determine if individuals with medically refractory migraine headache have volume or diffusion abnormalities on neuroimaging compared to neurotypical individuals.
Learn More >Chronic pain and reward processing are understood to be reciprocally related to one another. Previous studies of reward processing in chronic pain patients have reported incongruent findings. While several factors likely contribute to these disparate findings, these previous studies did not stratify their analyses by sex-a factor previously shown to robustly impact reward-related responses. Thus, we examined sex as a factor of interest in level of striatal activation during anticipation of monetary incentives among patients with chronic non-specific back pain and healthy controls (HC). This study utilized functional magnetic resonance imaging during a monetary incentive delay task to evaluate reward and loss responsivity in the striatum among males and females with and without chronic pain ( = 90). Group, sex, and group-by-sex interactions were analyzed repeated measures analysis of variance. Among HC, males exhibited significantly greater blood oxygen level dependent (BOLD) signal in the striatum during reward anticipation, particularly during large reward trials. By contrast, no significant sex differences were observed among patients. A significant group-by-sex interaction was also observed, revealing diminished BOLD responses among males with chronic pain relative to control males. These results provide novel evidence of sex-specific reductions in anticipatory responses to reward in patients with chronic pain. Altered striatal reward responsivity among males, but not females, suggests that the reward systems of males and females are uniquely disrupted by chronic pain, and highlights the value of including sex as a factor of interest in future studies of reward responsivity in the context of persistent pain.
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