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Intervertebral disc degeneration (IDD) is the basic pathological process of many degenerative diseases of the spine, characterized by series of symptoms, among which low back pain (LBP) is the most common symptom that patients suffer a lot, which not only makes patients and individual families bear a huge pain and psychological burden, but also consumes a lot of medical resources. IDD is usually thought to be relevant with various factors such as genetic predisposition, trauma and aging, and IDD progression is tightly relevant with structural and functional alterations. IDD processes are caused by series of pathological processes, including oxidative stress, matrix decomposition, inflammatory reaction, apoptosis, abnormal proliferation, cell senescence, autophagy as well as sepsis process, among which the oxidative stress and inflammatory response are considered as key link in IDD. The production and clearance of ROS are tightly connected with oxidative stress, which would further simulate various signaling pathways. The phenotype of disc cells could change from matrix anabolism-to matrix catabolism- and proinflammatory-phenotype during IDD. Recent decades, with the relevant reports about oxidative stress and inflammatory response in IDD increasing gradually, the mechanisms researches have attracted much more attention. Consequently, this study focused on the indispensable roles of the oxidative stress and inflammatory response (especially macrophages and cytokines) to illustrate the origin, development, and deterioration of IDD, aiming to provide novel insights in the molecular mechanisms as well as significant clinical values for IDD.
Learn More >Patient engagement (PE) in research refers to partnering with people with lived experience (e.g., patients, caregivers, family) as collaborators in the research process. Although PE is increasingly being recognized as an important aspect of health research, the current state of PE among pain research trainees in Canada is unclear.
Learn More >As an immune dysregulation-related disease, although ulcerative colitis (UC) primarily affects the intestinal tract, extraintestinal manifestations of the disease are evident, particularly in the oral cavity. Herein, we have reviewed the various oral presentations, potential pathogenesis, and treatment of oral lesions related to UC. The oral manifestations of UC include specific and nonspecific manifestations, with the former including pyostomatitis vegetans and the latter encompassing recurrent aphthous ulcers, atrophic glossitis, burning mouth syndrome, angular cheilitis, dry mouth, taste change, halitosis, and periodontitis. Although the aetiology of UC has not been fully determined, the factors leading to its development include immune system dysregulation, dysbiosis, and malnutrition. The principle of treating oral lesions in UC is to relieve pain, accelerate the healing of lesions, and prevent secondary infection, and the primary procedure is to control intestinal diseases. Systemic corticosteroids are the preferred treatment options, besides, topical and systemic administration combined with dietary guidance can also be applied. Oral manifestations of UC might accompany or precede the diagnosis of UC, albeit with the absence of intestinal symptoms; therefore, oral lesions, especially pyostomatitis vegetans, recurrent aphthous ulcer and periodontitis, could be used as good mucocutaneous signs to judge the occurrence and severity of UC, thus facilitating the early diagnosis and treatment of UC and avoiding severe consequences, such as colon cancer.
Learn More >Low back pain (LBP) is a chronic condition that causes great individual suffering and economic burden. The major contributor of LBP is intervertebral disc degeneration (IDD), which is caused by a spectrum of homeostasis alteration, including the apoptosis of nucleus pulposus (NP) and annulus fibrosus (AF) cells, degradation of extracellular matrix (ECM), calcification of cartilaginous endplates (CEP) and so on. Currently, the therapeutic strategy for IDD includes conservative and surgery treatment. Nevertheless, none of them could reverse the progressive destruction of the intervertebral disc. Hence, it is pivotal to pursue a new therapeutic approach. Exosomes, nano-sized substances with diameters of 30-150 nm, can be synthesized and secreted by various types of cells. They play an important role in intercellular communication. Increasing evidence implicates that exosomes could impact the intracellular transcription activities, thereby inhibiting or accelerating the proliferation and apoptosis of cells. Thus, it is a new therapeutic source for IDD. This review chiefly focuses on generalizing and clarifying the roles of exosomes in the onset and deterioration of IDD, and their therapeutic potential.
Learn More >Mosquito bites are endured by most populations worldwide. Reactions to mosquito bites range from localized wheals and papules with associated pruritus to rare systemic reactions and anaphylaxis in certain populations. The mechanism of itch is due to introduction of mosquito saliva components into the cutaneous tissue, although the exact pathophysiology is unclear. Histamine is thought to be a key player through mosquito saliva itself or through activation of mast cells by IgE or through an IgE-independent pathway. However, other salivary proteins such as tryptase and leukotrienes may induce non-histaminergic itch. Some individuals have a genetic predisposition for mosquito bites, and people with hematologic cancers, HIV, and other conditions are susceptible to robust reactions. Prevention of mosquito bites is key with physical barriers or chemical repellents. Treatment consists of second-generation antihistamines and topical corticosteroids. Further research on topical treatments that target neural-mediated itch is needed.
Learn More >Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition.
Learn More >Trigeminal neuralgia (TN) is a peripheral nerve disorder often accompanied by abnormalities in mood. The lateral habenula (LHb) plays important roles in the modulation of pain and emotion. In the present study, we investigated the involvement of the LHb in the mechanisms underlying allodynia and anxiety induced by partial transection of the infraorbital nerve (pT-ION) in mice. Our results indicated that pT-ION induced persistent orofacial allodynia and anxiety-like behaviors, which were correlated with increased phosphorylation of N-Methyl D-aspartate receptor (NMDAR) subtype 2B (p-NR2B) and Ca/calmodulin-dependent protein kinase II (p-CaMKII) in LHb neurons. Bilateral inhibition of NMDARs and CaMKII in the LHb attenuated the allodynia and anxiety-like behavior induced by pT-ION. Furthermore, bilateral activation of NMDARs in the LHb increased the expression of p-NR2B and p-CaMKII and induced orofacial allodynia and anxiety-like behaviors in naive mice. Adeno-associated virus (AAV)-mediated expression of hM3D(Gq) in CaMKII neurons of the bilateral LHb, followed by clozapine-N-oxide (CNO) administration, also triggered orofacial allodynia and anxiety-like behaviors in naïve mice with successful virus infection in LHb neurons (verified based on immunofluorescence). In conclusion, these findings suggest that activation of NMDA/CaMKII signaling in the LHb contributes to the occurrence and development of TN and related anxiety-like behaviors. Therefore, suppressing the activity of CaMKII neurons in the bilateral LHb by targeting NMDA/CaMKII may represent a novel strategy for treating pain and anxiety associated with TN.
Learn More >The standard of care paradigm for migraine treatment has been based almost exclusively on approaches that grew out of the happenstance use of market pharmaceuticals. Only methysergide, which has long since been removed from use for safety concerns, the ergotamine family of drugs, and the triptans were explicitly developed with migraine and other vascular headaches in mind. While the forward and innovative thinking to utilize the broad array of agents to treat migraine served millions well, their therapeutic efficacy was often low, and adverse event profiles were troublesome in the least. Advances in biochemical and molecular biology and the application of advanced "designing drugs" methods have brought about a potentially significant shift in treatment. The gepants have efficacies similar to the triptans but without vascular safety or medication overuse concerns. Preventative gepants offer innovative approaches to prevention and efficacy that exceed even the CGRP monoclonal antibodies. Those monoclonal antibodies brought rapid and highly effective outcomes across the spectrum of migraine. They outpaced older oral medication efficacy and eliminated most adverse events while potentially improving compliance with monthly or quarterly dosing. Other serotonin receptors beyond the 5HT1B and1D receptors have been targeted for decades. They now lead us to better formulations of dihydroergotamine for efficacy, convenience, and tolerability, and a 5HT1F-specific acute treatment like the gepants opens new options for acute management. Neuromodulation goes back to the mid-1800's. Our improved understanding of applied biomedical engineering has brought forward several tantalizing devices, including the application of currents distant from the target and patient regulated. Whether these advances change the paradigm of migraine treatment and standards of care remains to be seen, and issues such as cost and patient acceptance will help mold it.
Learn More >Tension-type headache (TTH) is the most prevalent headache in the clinical practice, leading to impaired social activities, work-related disability, and heavy financial burdens. Previous studies have described possible inducement, potential pathophysiology, and clinical management of TTH; however, due to the lack of attention, literature involving bibliometric analysis is sporadic. Therefore, this study aimed to explore the current hotspots and future directions of the TTH field by bibliometric analysis.
Learn More >Interstitial cystitis/bladder pain syndrome (IC/BPS) is an immense burden to both patients and the American healthcare system; it is notoriously difficult to diagnose. Prevalence estimates vary widely (150-fold range in women and >500-fold range in men).
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