TRPV1: Receptor structure, activation, modulation and role in neuro-immune interactions and pain

Cell Calcium, Journal Year: 2024, Volume and Issue: 119, P. 102870 - 102870

Published: March 8, 2024

Language: Английский

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Injectable Affinity and Remote Magnetothermal Effects of Bi‐Based Alloy for Long‐Term Bone Defect Repair and Analgesia

Advanced Science, Journal Year: 2021, Volume and Issue: 8(14)

Published: May 20, 2021

Abstract As alternatives, metallic/nonmetallic bone graft materials play significant roles in defect surgery to treat external trauma or disease. However, date, there are rather limited long‐term implantable owning situ molding incapability of metallics and poor mechanical property nonmetallics. Here, Bi‐based low melting point alloy, with unique properties injectability, solid‐liquid phase transition, capability, biocompatibility, present obvious long‐lasting affinity as the excellent artificial bone‐substitute. It is particularly necessary out that targeted injected Bi alloy remains its original position for up 210 days without moving, well as, displays good osseointegration ability resolve repeated revision caused by losing repair material. Additionally, outstanding electrical thermal conductivity, an unconventional way using realize very beneficial hyperthermia analgesia via non‐invasive wireless energy delivery first proposed, which avoids adverse effects on remodeling inflicted traditional drugs. The significantly decreased expression pain sensitizing factor, such interleukin‐6, neuropeptide substance, transient receptor potential vanilloid 1 reveals mechanism analgesia. findings suggest combination therapy analgesia, owns far‐reaching clinical application value.

Language: Английский

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Unlocking the potential of TRPV1 based siRNA therapeutics for the treatment of chemotherapy-induced neuropathic pain

Life Sciences, Journal Year: 2021, Volume and Issue: 288, P. 120187 - 120187

Published: Nov. 30, 2021

Language: Английский

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HBO treatment enhances motor function and modulates pain development after sciatic nerve injury via protection the mitochondrial function

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Aug. 15, 2023

Peripheral nerve injury can cause neuroinflammation and neuromodulation that lead to mitochondrial dysfunction neuronal apoptosis in the dorsal root ganglion (DRG) spinal cord, contributing neuropathic pain motor dysfunction. Hyperbaric oxygen therapy (HBOT) has been suggested as a potential therapeutic tool for injury. However, specific cellular molecular mechanism by which HBOT modulates development of through protection is still unclear.Mechanical thermal allodynia function were measured rats following sciatic crush (SNC). The HBO treatment (2.5 ATA) was performed 4 h after SNC twice daily (12 intervals) seven consecutive days. To assess cord (L2-L6), high-resolution respirometry on day 7 using OROBOROS-O2k. In addition, RT-PCR Immunohistochemistry at end experiment neuroinflammation, neuromodulation, DRG (L3-L6) (L2-L6).HBOT during early phase alleviates mechanical hypersensitivity Moreover, stress, cord. Thus, we found significant reduction presence macrophages/microglia MMP-9 expression, well transcription pro-inflammatory cytokines (TNFa, IL-6, IL-1b) (IL6) group treated with compared untreated group. Notable, overexpression TRPV1 channel, high Ca2+ permeability, reduced along marker (cleaved-Caspase3) stress (TSPO) Additionally, prevents respiration, including non-phosphorylation state, ATP-linked maximal respiration SNC.Mitochondrial peripheral be mediated neuromodulation. Strikingly, our findings indicate critical period transition from acute chronic via reducing protecting function, consequently preventing

Language: Английский

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SIRT1 mediates the excitability of spinal CaMKIIα‐positive neurons and participates in neuropathic pain by controlling Nav1.3

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(6)

Published: June 1, 2024

Neuropathic pain is a common chronic disorder, which largely attributed to spinal central sensitization. Calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) activation in the dorsal horn (SDH) major contributor However, exact way that CaMKIIα-positive (CaMKIIα

Language: Английский

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The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Sept. 9, 2024

The transient receptor potential vanilloid 1 (TRPV1) channel plays a dual role in peripheral neuropathic pain (NeuP) by acting as “pain switch” through its sensitization and desensitization. Hyperalgesia, commonly resulting from tissue injury or inflammation, involves the of TRPV1 channels, which modulates sensory transmission primary afferent nociceptors to spinal dorsal horn neurons. In chemotherapy-induced neuropathy (CIPN), is implicated mechanisms due interaction with ion neurotransmitter signaling, oxidative stress. Sensitization root ganglion neurons contributes CIPN development, inhibition channels can reduce mechanical hypersensitivity. diabetic (DPN), involved modulation pathways including reactive oxygen species cytokine production. TRPV1’s TRPA1 further influences chronic onset progression. Therapeutically, capsaicin, agonist, induce analgesia desensitization, while antagonists siRNA targeting show promise preclinical studies. Cannabinoid provides another pathway for alleviating pain. This review summarizes recent research on association NeuP.

Language: Английский

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The LRP1-SHP2 pathway regulates TRPV1 sensitivity in the peripheral nervous system: Insights from amyloid beta 1–42 modulation

Journal of Advanced Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Mature adults often exhibit higher pain thresholds than younger individuals. However, this phenomenon is poorly understood, especially with regards to peripheral nervous system signaling. We investigated the involvement of amyloid beta (Aβ) in regulating heat sensitivity within dorsal root ganglion (DRG) during adult maturation. employed various vivo and vitro techniques investigate modulatory effect Aβ1-42. Heat alteration was examined spared nerve injury (SNI) models young mature Aβ1-42-treated mice. Phosphorylation receptor inhibition assays were performed elucidate molecular mechanisms involved pathway interactions vitro. mice had thermal elevated levels Aβ1-42 compared In analyses indicated that Aβ1-42-induced activation low-density lipoprotein receptor-related protein 1 (LRP1) led phosphorylation src-homology domain-2-containing tyrosine phosphatase 2 (SHP2), which turn inhibited transient potential vanilloid (TRPV1) function primary DRG neurons. Similar observed human Additionally, α2-macroglobulin (α2M), a potent LRP1 agonist, also TRPV1 activity reduced through LRP1-SHP2 pathway. studies mouse SNI model demonstrated intraplantar injection α2M enhanced paw withdrawal latency; these effects reversed by protein-associated 1. The findings suggest crucial role Aβ modulating maturation inhibition. study offers new insights into regulation process revealing novel intrinsic mechanism involving its LRP1/SHP2 adults. This could be therapeutic target for age-related chronic management.

Language: Английский

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Cytokine activin C ameliorates chronic neuropathic pain in peripheral nerve injury rodents by modulating the TRPV1 channel

British Journal of Pharmacology, Journal Year: 2020, Volume and Issue: 177(24), P. 5642 - 5657

Published: Oct. 23, 2020

The cytokine activin C is mainly expressed in small-diameter dorsal root ganglion (DRG) neurons and suppresses inflammatory pain. However, the effects of neuropathic pain remain elusive. Male rats wild-type TRPV1 knockout mice with peripheral nerve injury - sciatic axotomy spinal ligation rats; chronic constriction (CCI) provided models Ipsilateral lumbar (L)4-5 DRGs were assayed for expression. Chronic animals treated intrathecal or locally pre-administered vehicle. Nociceptive behaviours pain-related markers L4-5 cord evaluated. channel modulation by was measured. Following injury, expression βC subunit mRNA protein markedly up-regulated axotomy, SNL CCI. [Correction added on 26 November 2020, after first online publication: preceding sentence has been corrected this current version.] Intrathecal dose-dependently inhibited ligated rats. Local pre-administration decreased pain, macrophage infiltration into ipsilateral microglial reaction cords In rat DRG neurons, enhanced capsaicin-induced currents. Pre-treatment reduced capsaicin-evoked acute hyperalgesia normalized persistent hypothermia mice. Finally, analgesic effect abolished Activin inhibits modulating channels, revealing potential applications therapy.

Language: Английский

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Current insights and therapeutic strategies for targeting TRPV1 in neuropathic pain management

Life Sciences, Journal Year: 2024, Volume and Issue: 355, P. 122954 - 122954

Published: Aug. 10, 2024

Neuropathic pain, a common symptom of several disorders, exerts substantial socioeconomic burden worldwide. Transient receptor potential vanilloid 1 (TRPV1), non-selective cation channel predominantly ex-pressed in nociceptive neurons, plays pivotal role nociception, by detecting various endogenous and exogenous stimuli, including heat, pro-inflammatory mediators, physical stressors. Dysregulation TRPV1 signaling further contributes to the pathophysiology neuropathic pain. Therefore, targeting is promising strategy for developing novel analgesics with improved efficacy safety profiles. Several pharmacological approaches modulate activity, agonists, antagonists, biological RNA interference (RNAi, small interfering [siRNA]) have been explored. Despite preclinical success, clinical translation TRPV1-targeted therapies has encountered challenges, hyperthermia, hypothermia, pungency, desensitization. Nevertheless, ongoing research efforts aim refine interventions through structural modifications, development selective modulators, discovery natural, peptide-based drug candidates. Herein, we provide guidance researchers clinicians involved new specifically reviewing existing literature highlighting current activities. This study discusses future endeavors enhancing efficacy, safety, tolerability candidates, thereby facilitates these discoveries into effective alleviate pain disorders.

Language: Английский

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Role of TRP Channels in Cancer-Induced Bone Pain

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1229 - 1229

Published: Jan. 30, 2025

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase mortality morbidity. management cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use burdened by a number possible side effects. Moreover, recent progresses treatment increased life expectancy patients, even those with metastatic disease. In this narrative review, we reported main findings regarding TRP channel function models. cation channels play key role different functions cells, including regulation their potential for metastasization, are involved pathways perception, through peripheral central Genetic deletion decreased sensitivity following tumour cell inoculation. Preclinical data suggest modulators some channels, such as TRPV1, TRPA1, TRPM7 TRPM8. Clinical results scarce; however, physiological modulating remodelling involvement preclinical models have garnered interest areas research last few years, innovative analgesic strategies that may overcome long-term effects opioids.

Language: Английский

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