Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders

Journal of Neuroinflammation, Год журнала: 2025, Номер 22(1)

Опубликована: Фев. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Язык: Английский

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Neuropathic Pain: A Comprehensive Bibliometric Analysis of Research Trends, Contributions, and Future Directions

Current Pain and Headache Reports, Год журнала: 2025, Номер 29(1)

Опубликована: Апрель 4, 2025

Язык: Английский

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Exploring the Therapeutic Potential of Psychedelics in Chronic Pain Management: A New Frontier in Medicine

Neuroscience Bulletin, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Язык: Английский

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Sprouting sympathetic fibres release CXCL16 and norepinephrine to synergistically mediate sensory neuronal hyperexcitability in a rodent model of neuropathic pain

British Journal of Anaesthesia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Chronic neuropathic pain generally has a poor response to treatment with conventional drugs. Sympathectomy can alleviate in some patients, suggesting that abnormal sympathetic-somatosensory signaling interactions might underlie forms of pain. The molecular mechanisms underlying remain obscure. Lumbar sympathectomy was performed spared nerve injury (SNI) mice or rats, and the up-down method used measure mechanical paw withdrawal threshold. Dorsal root ganglia (DRG) injection perfusion were deliver virus Methylated RNA immunoprecipitation sequencing, RNA-sequencing, immunoelectron microscopy identify neurotransmitters. We found sprouting tyrosine hydroxylase-positive sympathetic fibres DRG mediated maintenance allodynia after SNI (day 28, P<0.001). further significantly increased N6-methyladenosine level CXCL16 messenger P<0.001), which attributable reduced demethylase fat mass obesity-associated protein (P=0.002) interaction YTHDF1 (P=0.013) ganglion. Enhanced expression lead increases release into act synergistically norepinephrine from terminals enhance neuronal excitability. Norepinephrine co-released contribute rodent model.

Язык: Английский

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GDF11 Mitigates Neuropathic Pain via Regulation of Microglial Polarization and Neuroinflammation through TGF-βR1/SMAD2/NF-κB Pathway in Male Mice

Journal of Neuroimmune Pharmacology, Год журнала: 2025, Номер 20(1)

Опубликована: Фев. 12, 2025

Язык: Английский

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Targeting connexins: possible game changer in managing neuropathic pain?

Trends in Molecular Medicine, Год журнала: 2024, Номер 30(7), С. 642 - 659

Опубликована: Апрель 8, 2024

Язык: Английский

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Sustained Release of αO-Conotoxin GeXIVA[1,2] via Hydrogel Microneedle Patch for Chronic Neuropathic Pain Management

Marine Drugs, Год журнала: 2025, Номер 23(4), С. 161 - 161

Опубликована: Апрель 7, 2025

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed sustained-release hydrogel microneedle patch encapsulating to address these challenges. Optimized 4:3 (w/w) polyvinyl alcohol (PVA)–sucrose formulation achieved 98.6% structural integrity controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, single increased mechanical paw withdrawal thresholds 0.056 g 0.7269 g, maintaining efficacy for 3 days. constriction (CCI) models showed comparable relief. Notably, treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 untreated). platform extends GeXIVA[1,2]’s duration hours days through sustained release, while resolving administration challenges transdermal delivery, expanding the potential applications GeXIVA[1,2], demonstrating promising strategy chronic management.

Язык: Английский

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

Molecules, Год журнала: 2023, Номер 28(15), С. 5766 - 5766

Опубликована: Июль 30, 2023

Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate this type chronic with complex mechanism tends to worsen over time, leading significant deterioration in patients’ quality life and issues like depression, disability, disturbed sleep. Presently used analgesics are not effective enough neuropathy treatment may cause many side effects due the high doses needed. In recent years, researchers have pointed important role chemokines only development maintenance but also effectiveness analgesic drugs. Currently, approximately 50 known act through 20 different seven-transmembrane G-protein-coupled receptors located on surface neuronal, glial, immune cells. Data from years clearly more than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting synthesis, or brings neuropathic relief. Several them (CCL1/2/3/7/9/XCL1) been shown be able reduce opioid drug neuropathy, antibodies against can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence chemokine promising targets for pharmacotherapy; receptor antagonists relieve etiologies, most enhance analgesia, example, blockade CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), XCR1 (vMIP-II). Recent has multitarget receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), CCR2/CCR5/CCR8 (RAP-103), very painkillers. A multidirectional strategy based modulation neuronal–glial–immune interactions changing activity family significantly improve patients suffering pain. However, members still underestimated pharmacological treatment. article, we review literature provide new insights into

Язык: Английский

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Genetic insights into associations of multisite chronic pain with common diseases and biomarkers using data from the UK Biobank

British Journal of Anaesthesia, Год журнала: 2023, Номер 132(2), С. 372 - 382

Опубликована: Дек. 15, 2023

Язык: Английский

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Transient Receptor Potential Channels: Multiple Modulators of Peripheral Neuropathic Pain in Several Rodent Models

Neurochemical Research, Год журнала: 2024, Номер 49(4), С. 872 - 886

Опубликована: Янв. 28, 2024

Язык: Английский

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