Neuropathic pain; what we know and what we should do about it

Frontiers in Pain Research, Год журнала: 2023, Номер 4

Опубликована: Сен. 22, 2023

Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve promotes Schwann cell activation and invasion immunocompetent cells into site injury, spinal cord higher sensory structures such as thalamus cingulate cortices. Various cytokines, chemokines, growth factors, monoamines neuropeptides effect two-way signalling between neurons, glia immune cells. This sustained hyperexcitability spontaneous activity in primary afferents that crucial for onset persistence well misprocessing information supraspinal structures. Much current understanding aetiology identification drug targets derives studies consequences peripheral rodent models. Although a vast amount has been forthcoming, translation this clinical arena minimal. Few, if any, major therapeutic approaches have appeared since mid 1990's. may reflect failure recognise differences processing males vs. females, cellular responses different types humans animals. Basic science which seek bridge knowledge gap include better assessment animal models, use models emulate human disease, stratification phenotypes according quantitative signs symptoms disease. lead more personalized effective treatments individual patients. Significance statement: There an urgent need find new neuropathic pain. classical revealed essential features central sensitization some molecular mechanisms involved, they do not adequately model multiplicity states injuries bring forth clinic. review seeks integrate disciplines understand pain; including immunology, biology, electrophysiology biophysics, anatomy, neurology, pharmacology behavioral science. Beyond this, it underlines ongoing refinements basic practice will engender improved management.

Язык: Английский

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BDNF in Neuropathic Pain; the Culprit that Cannot be Apprehended

Neuroscience, Год журнала: 2024, Номер 543, С. 49 - 64

Опубликована: Фев. 28, 2024

Язык: Английский

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EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain

Cells, Год журнала: 2023, Номер 12(7), С. 1058 - 1058

Опубликована: Март 31, 2023

Recent studies by us and others have shown that enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, in glial cells regulates the genesis neuropathic pain modulating production proinflammatory cytokines chemokines. In this review, we summarize recent advances research area. EZH2 is subunit polycomb repressive complex 2 (PRC2), which primarily serves as methyltransferase to catalyze methylation 3 on lysine 27 (H3K27), ultimately resulting transcriptional repression. Animals with exhibit increased activity neuroinflammation injured nerve, spinal cord, anterior cingulate cortex. Inhibition DZNep or GSK-126 ameliorates pain. protein expression increases upon activation Toll-like receptor 4 calcitonin gene-related peptide receptors, downregulation miR-124-3p miR-378 microRNAs, upregulation Lncenc1 MALAT1 long noncoding RNAs. Genes suppressed include suppressor cytokine signaling (SOCS3), nuclear factor (erythroid-derived 2)-like-2 (NrF2), miR-29b-3p, miR-146a-5p, brain-specific angiogenesis inhibitor 1 (BAI1). Pro-inflammatory mediators facilitate neuronal along pain-signaling pathways sensitizing nociceptors periphery, well enhancing excitatory synaptic activities suppressing inhibitory CNS. These collectively reveal implicated known be key players process Therefore, targeting pathway may open new avenue mitigate

Язык: Английский

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Environmental enrichment for neuropathic pain via modulation of neuroinflammation

Frontiers in Molecular Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Март 21, 2025

Neuropathic pain causes tremendous biological and psychological suffering to patients worldwide. Environmental enrichment (EE) is a promising non-pharmacological strategy with high cost-effectiveness reduce neuropathic support rehabilitation therapy. Three researchers reviewed previous studies determine the efficacy of EE for research how improves through neuroinflammation. For this review, Embase, PubMed, Cochran were searched. authors did study selection data extraction. Out 74 papers, 7 met inclusion criteria. In chronic constriction injury rats acute or detrimental stimulation, change behavior was influenced by environmental settings like start time, cage size. Besides, physical has larger effect than socially in inflammatory pain. These articles suggest employing various regulate release pain-causing substances changes ion channels peripheral central nerves improve depression anxiety conditions. The existing proof provides important knowledge upcoming preclinical investigations practical use clinical treatment. This analysis aids advancement improved approaches managing pain, focus on internal mechanisms controlling

Язык: Английский

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BDNF/TrkB signaling pathway and WDR neurons: Core factors inducing central sensitization of neuropathic pain

Life Sciences, Год журнала: 2025, Номер 377, С. 123796 - 123796

Опубликована: Июнь 4, 2025

Язык: Английский

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IUPHAR review- Preclinical models of neuropathic pain: Evaluating multifunctional properties of natural cannabinoid receptors ligands

Pharmacological Research, Год журнала: 2023, Номер 199, С. 107013 - 107013

Опубликована: Ноя. 25, 2023

Neuropathic pain remains prevalent and challenging to manage is often comorbid with depression anxiety. The new approach that simultaneously targets neuropathic the associated comorbidities, such as anxiety, timely critical, given high prevalence severity of lack effective analgesics. In this review, we focus on animal models researchers have used investigate analgesic effects cannabidiol (CBD) Beta-Caryophyllene (BCP) individually in combination while addressing impact these compounds major comorbidity (e.g., depression, anxiety) pain. We also addressed potential targets/mechanisms by which CBD BCP produce models. preclinical studies examined review support combined alternative analgesics for showing beneficial

Язык: Английский

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Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(7), С. 3602 - 3602

Опубликована: Март 22, 2024

Patients with systemic lupus erythematosus (SLE) frequently experience chronic pain due to the limited effectiveness and safety profiles of current analgesics. Understanding molecular synaptic mechanisms underlying abnormal neuronal activation along signaling pathway is essential for developing new analgesics address SLE-induced pain. Recent studies, including those conducted by our team others using SLE animal model (MRL/lpr lupus-prone mice), have unveiled heightened excitability in nociceptive primary sensory neurons within dorsal root ganglia increased glutamatergic activity spinal horn neurons, contributing development mice SLE. Nociceptive animals exhibit elevated resting membrane potentials, reduced thresholds rheobases action potentials. These changes coincide production TNFα IL-1β, as well ERK ganglion, coupled decreased AMPK same region. Dysregulated linked animals. Additionally, characterized enhanced presynaptic glutamate release postsynaptic AMPA receptor activation, alongside glial transporters. alterations are caused activities IL-18, CSF-1, thrombin, horn. Furthermore, pharmacological GPR109A receptors microglia suppresses inhibiting p38 MAPK both IL-1β reducing findings collectively unveil crucial targets modulating periphery horn, offering insights into managing

Язык: Английский

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Sigma-1 receptor targeting inhibits connexin 43 based intercellular communication in chronic neuropathic pain

Inflammation Research, Год журнала: 2024, Номер 73(10), С. 1711 - 1726

Опубликована: Авг. 2, 2024

Neuropathic pain is a chronic condition characterized by aberrant signaling within the somatosensory system, affecting millions of people worldwide with limited treatment options. Herein, we aim at investigating potential sigma-1 receptor (σ1R) antagonist in managing neuropathic pain.

Язык: Английский

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Spatial, transcriptomic, and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition

Cell Reports, Год журнала: 2024, Номер 43(11), С. 114876 - 114876

Опубликована: Окт. 24, 2024

Язык: Английский

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Cellular and Molecular Organization of the Rhesus Macaque Dorsal Horn with Comparison to Mouse

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Апрель 5, 2022

Summary Key mechanisms underlying chronic pain occur within the neural circuitry of dorsal horn. Recent genome-wide association studies (GWAS) have identified genetic variants associated with predisposition to pain. However, most these lie in regulatory non-coding regions that so far not been linked spinal cord function. Here, we take a multi-species approach determine whether impact elements horn neurons. We first built more comprehensive single cell atlas; filling gaps by generating high-quality Rhesus macaque atlas and integrating it human mouse. With cellular-resolution spatial transcriptomics, mapped laminar distributions resulting species-conserved neuron subtypes, uncovering an unexpected organization. Lastly, generated mouse single-nucleus open chromatin partition heritability traits. From this, strong, selective associations between specific, conserved subtypes major forms

Язык: Английский

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