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A comprehensive review on pain: Model, target, therapy, and prospect (Review).

Pain serves as both a protective physiological response essential for species survival and a global health issue affecting human well‑being and societal development. The present review systematically summarized and analyzed the research progresses on pain through a multidimensional analytical framework encompassing animal models, molecular targets, therapeutic approaches and future prospects. In animal modeling, neuropathic pain paradigms have evolved from traditional mechanical compression to composite models that combine dynamic displacement and chemical stimulation. Cancer‑induced pain mode

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… In reward circuits, MOR activation in ventral tegmental area-nucleus accumbens dopaminergic projections disinhibited GABAergic neurons to enhance dopamine release and addiction potential ( 195 ). Molecularly, opioid receptors signal through inhibitory G protein and β-arrestin pathways. …

Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic

Регулирование питания иммунной системы кишечного мозга происходит на протяжении всей жизни.

Иммунная ось кишечника объединяет микробные, иммунные и нейронные сигналы для регулирования нейроразвития, гомеостаза и подверженности болезням. Раннее питание, в частности молочные олигозакариды, формирует благотворный микробиотический состав, повышает гиппокампальную пластичность, способствует антивоспалительной микроглианской поляризации и поощряет иммунную терпимость. Микробиота - метаболиты гута, включая короткоцепные жирные кислоты, производные триптофана и вторичные желчные кислоты, регулируют микроглиатическое созревание, функцию астроцита, дифференциацию клеток Т, производство нейротр

Нанозимы: инновационная терапия в борьбе с нейродегенеративными заболеваниями.

Нейродегенеративные заболевания, включая болезнь Альцгеймера (AD), болезнь Паркинсона (PD), множественный склероз (MS), амиотропический боковой склероз (ALS) и болезнь Хантингтона (HD), представляют собой серьезную проблему для здоровья населения мира из-за их прогрессивного характера и отсутствия лечения. Эти расстройства характеризуются окислительным стрессом, завязыванием белка и нейроинфламмацией, которые в совокупности приводят к нервным повреждениям и смерти. Последние достижения в нанотехнологии позволили внедрить нанозменные наноматериалы, которые имитируют деятельность, похожую на фер

Regulatory role of PI3K/Akt/WNK1 signal pathway in mouse model of bone cancer pain.

In the advanced stage of cancer, the pain caused by bone metastasis is unbearable, but the mechanism of bone cancer pain (BCP) is very complicated and remains unclear. In this study, we used 4T1 mouse breast cancer cells to establish a bone cancer pain model to study the mechanism of BCP. Then the paw withdrawal mechanical threshold (PWMT) and the hematoxylin-eosin staining were used to reflect the erosion of cancer cells on tibia tissue. We also determined the role of proinflammatory factors (TNF-α, IL-17, etc.) in BCP by the enzyme-linked immunosorbent assay in mouse serum. When GSK690693, a

Obesity: pathophysiology and therapeutic interventions.

Over the past few decades, obesity has transitioned from a localized health concern to a pressing global public health crisis affecting over 650 million adults globally, as documented by WHO epidemiological surveys. As a chronic metabolic disorder characterized by pathological adipose tissue expansion, chronic inflammation, and neuroendocrine dysregulation that disrupts systemic homeostasis and impairs physiological functions, obesity is rarely an isolated condition; rather, it is frequently complicated by severe comorbidities that collectively elevate mortality risks. Despite advances in nutr

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t

Животные модели периферической нейропатии, вызванной химиотерапией, для гематологических заболеваний: обзор.

Химиотерапия это one основные виды лечения гематологовых магнестов. Однако периферическая нейропатия, вызванная химиотерапией (CIPN) one Наиболее часто встречающиеся долгосрочные токсичные реакции в химиотерапии, а также случаи CIPN влияют на качество жизни пациентов и могут приводить к прерыванию химиотерапии в тяжелых случаях, снижая тем самым эффективность химиотерапии. В настоящее время мы резюмируем существующие зверские модели CIPN, включая характеристики нескольких общих животных моделей, таких, как периферическая нейропатия, вызванная бортезомибами, периферическая нейропатия, вызванная

Cancer Pain Is Not One-Size-Fits-All: Evolving from Tradition to Precision.

Cancer pain remains a significant challenge in oncology, profoundly affecting patients' quality of life, function, and prognosis. Historically under-recognized and managed with a uniform, opioid-centric approach, cancer pain was often inadequately treated. Advances in pain assessment, multimodal analgesia, and supportive care have improved outcomes, yet traditional algorithms frequently fail to address the complex, heterogeneous nature of cancer pain. Contemporary management is shifting toward precision and personalized medicine, integrating genetic, molecular, and biomarker data with individu

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… Opioids bind to MORs (key modulators in the reward circuitry) on inhibitory GABAergic neurons in the VTA, disinhibiting dopaminergic neurons and causing excessive dopamine release in the NAc, which produces intense euphoria and reinforcement. …

Оптический анализ функционального воздействия демиелинации и ремиэлизации Cuprizone на межсферную нервную коммуникацию в антериорной кортекс через Corpus Callosum.

Cuprizone (CPZ) — широко используемый токсин, который вызывает демиелинизирующие заболевания в моделях животных, производя множественный склероз (MS), похожий на патологию в грызунах. CPZ является одним из немногих токсинов, которые вызывают демиелинацию и последующее воспоминание после прекращения ее применения. В этом исследовании рассматриваются функциональные последствия демиэлизации, вызванной КПЗ, и последующее восстановление нейронной связи в передней коре сингула (АКК) с уделением особого внимания соединению между полушариями через корпус каллосум (CC). Используя широкополосную высокос

The Role of Inflammation in Tinnitus: A Systematic Review and Meta-Analysis.

Subjective tinnitus is the perception of sound without the presence of an external source. Increasing evidence suggests that tinnitus is associated with inflammation. In this systematic review, the role of inflammation in subjective tinnitus was studied. Nine animal and twenty human studies reporting inflammatory markers in both humans and animals with tinnitus were included. It was established that TNF-α and IL-1β are increased in tinnitus, and that microglia and astrocytes are activated as well. Moreover, platelet activation may also play a role in tinnitus. In addition, we elaborate on mech

Нейрофармакология каннабиноидов: всеобъемлющий обзор доклинических и клинических данных о экстрактах гемп-деривных веществ и активных соединениях.

Каннабис сатива содержит более 120 фитоканнабиноидов, причем наиболее характерными из них являются Δ9-тетрагидроканнабинол (THC) и каннабидиол (CBD). В настоящем обзоре обобщаются доклинические и клинические данные об экстрактах гематома, каннабиноидах и активных соединениях. THC действует главным образом как частичный агонист каннабиноидного рецептора типа 1 (CB1) и типа 2 (CB2), приводящий к психоактивным, аппетитным, антиэметическим и анальгетическим эффектам. КБР не является опьяняющим и имеет мультимодальный профиль, включающий негативную аллостерическую модуляцию CB1, обратное агонизм CB

Cannabidiol (CBD) in Cancer Management.

The plant Cannabis sativa has been in use medicinally for several thousand years. It has over 540 metabolites thought to be responsible for its therapeutic effects. Two of the key phytocannabinoids are cannabidiol (CBD) and tetrahydrocannabinol (THC). Unlike THC, CBD does not have potentially intoxicating effects. Preclinical and clinical research indicates that CBD has a wide range of therapeutic effects, and many of them are relevant to the management of cancer. In this article, we explore some of the potential mechanisms of action of CBD in cancer, and evidence of its efficacy in the integr

The Effect of Docosahexaenoic Acid and α-Lipoic Acid as Prevention of Bortezomib-Related Neurotoxicity in Patients With Multiple Myeloma.

Background and Aims: In cancer patients, a common complication during chemotherapy is chemotherapy-induced peripheral neuropathy (CIPN). For this reason, we decided to conduct a phase II prospective study on 33 patients with multiple myeloma at first diagnosis, to evaluate whether a nutraceutical compound given for 6 months during bortezomib (BTZ) treatment succeeded in preventing the onset of neurotoxicity. Methods: Neurological evaluation, electroneurography, and functional and quality of life (QoL) scales were performed at baseline and after 6 months. We administered a tablet containing doc

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy.

Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) ne

From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.

The stress response is essential for cellular and organismal survival as it acts as a protective and adaptive mechanism to maintain homeostasis. At the organismal level, physical stressors induce responses in mammals that are mediated primarily by the hypothalamic-pituitary-adrenal (HPA) axis, which regulates glucocorticoid secretion. The HPA axis functions as a circadian-regulated, multi-oscillator system, in which the paraventricular nucleus, the pituitary, and the adrenal gland exhibit intrinsic rhythmicity while remaining coordinated by the output from the suprachiasmatic nucleus. Glucocor

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… In parallel, CRH neurons have been implicated in circadian regulation of arousal, with inhibition from SCN GABAergic neurons gating CRH neuron firing across the day, while optogenetic activation of CRH neurons robustly promotes wakefulness through orexinergic pathways [ 15 ]. …

Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.

Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients' quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and ma

Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses.

In this review, we discuss the importance of capsaicin to the current understanding of neuronal modulation of pain and explore the mechanisms of capsaicin-induced pain. We will focus on the analgesic effects of capsaicin and its clinical applicability in treating pain. Furthermore, we will draw attention to the rationale for other clinical therapeutic uses and implications of capsaicin in diseases such as obesity, diabetes, cardiovascular conditions, cancer, airway diseases, itch, gastric, and urological disorders.

Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies.

BackgroundPeripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy.MethodThe current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of