Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment

Life, Journal Year: 2024, Volume and Issue: 14(8), P. 991 - 991

Published: Aug. 9, 2024

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, burning pain in the upper lower extremities. The pathophysiology not completely understood; however, it believed that chemotherapies induce via directly damaging mitochondria, impairing function ion channels, triggering immunological mechanisms, disrupting microtubules. treatment medical challenge, there are no approved pharmacological options. Currently, duloxetine other antidepressants, antioxidant, anti-inflammatory, ion-channel targeted therapies commonly used clinics to relieve symptoms CIPN. Several types such as cannabinoids, sigma−1 receptor antagonists, nicotinamides ribose, being evaluated preclinical clinical studies. This paper summarizes information related physiology medicines could be for treating this condition.

Language: Английский

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Peripheral, central, and chemotherapy-induced neuropathic changes in pancreatic cancer

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

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Entrectinib can induce nerve cell damage by inhibiting PI3K-AKT and TGF-β signaling pathways

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Background The tyrosine receptor kinase inhibitor (TRKi) entrectinib is used to treat neurotrophic (NTRK) fusion-positive solid tumors and ROS1-positive patients. Despite its impressive efficacy against cancer, the clinical application still limited by central nervous system (CNS)-related toxicities. However, precise mechanism of such CNS-related toxicities remains elusive. Methods effect entrectinib-induced nerve cell damage was evaluated cells (PC12, HT22 SK-N-SH) based in vitro models. Various assays, including CCK-8, colony formation EdU incorporation assays were utilized estimate cellular viability proliferation ability. Cell apoptosis measured flow cytometry. Next, transcriptome sequencing technology performed identify differentially expressed genes (DEGs). Gene ontology (GO), kyoto encyclopedia genomes (KEGG) analysis gene set enrichment (GSEA) applied predict potential functions DEGs. Quantitative real time polymerase chain reaction (qRT-PCR) Western blotting measure expressions thrombospondin-1 (THBS1), TGF-β1, PI3K, AKT phosphorylated (p-AKT) entrectinib-treated cells. Additionally, we Preliminary observed validated whether THBS1 overexpression could rescue abnormalities PI3K-AKT TGF-β signaling pathways. Results Entrectinib significantly inhibited formation, induced apoptosis. Transcriptome qRT-PCR revealed that downregulated within treatment. KEGG GSEA also suggested directly caused proliferation-related pathway like pathway, apoptosis-related pathway. We further demonstrated THBS1, p-AKT entrectinib. Meanwhile, pretreatment with plasmids rescued from death Conclusion These results identified a critical role promoting downregulating expression while inhibiting Our findings will provide therapeutic targets for

Language: Английский

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An integrated approach to rehabilitation of patients with chemotherapy-induced polyneuropathy. Current state of the problem

Восстановительные биотехнологии, профилактическая, цифровая и предиктивная медицина., Journal Year: 2025, Volume and Issue: 2(1), P. 34 - 34

Published: March 12, 2025

The authors summarize modern data on epidemiology, pathogenesis, drug and non-drug treatment prevention of progression chemo-induced polyneuropathy. Effectiveness isolated combined methods are considered, information about preclinical clinical studies is provided.

Language: Английский

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Phenyl-benzyl-ureas with pyridazinone motif: Potent soluble epoxide hydrolase inhibitors with enhanced pharmacokinetics and efficacy in a paclitaxel-induced neuropathic pain model

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117510 - 117510

Published: March 1, 2025

Language: Английский

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Contributions of synaptic energetic dysfunction by microtubule dynamics and microtubule‐based mitochondrial transport disorder to morphine tolerance

British Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: May 13, 2025

Abstract Background and Purpose Morphine is among the most powerful analgesic, but its long‐term use can cause tolerance. Synaptic ATP supply critical for maintaining synaptic transmission. Microtubule‐based mitochondrial transport ensures energy supply. How changes with morphine role of microtubule tracks in remain elusive. Chronic treatment destroy cytoskeletons. We investigated effect cytoskeleton on mechanism dynamics after exposure. Experimental Approach Rats were treated thermal pain thresholds was evaluated by tail‐flick latency test. Various antagonists agonists used elucidated microtubules tolerance vivo SH‐SY5Y cells. Key Results reduced production. Improving oxidative phosphorylation (OXPHOS) alleviated downregulation levels. Microtubule‐stabilizing agents prevented disruption ameliorated deficit via microtubule‐based transport. In cells, exposure expression. And re‐opening Ca 2+ channel agonist decrease calcium/calmodulin‐dependent protein kinase 2 (CAMKK2)/AMP‐activated (AMPK) pathway. Conclusion Implications This study demonstrates that regulated –CAMKK2–AMPK axis production, explaining an interplay between chronic morphine‐induced abnormal neuroadaptation energetic dysfunction. These findings implicated a potential clinical strategy prolonging opioid antinociceptive during control.

Language: Английский

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Effects of Swanson theory-based auricular acupressure on chemotherapy-induced peripheral neuropathy, and broader health-related outcomes in patients with breast cancer: a randomized controlled trial

Asia-Pacific Journal of Oncology Nursing, Journal Year: 2025, Volume and Issue: unknown, P. 100729 - 100729

Published: May 1, 2025

Language: Английский

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Centralizing the Knowledge and Interpretation of Pain in Chemotherapy-Induced Peripheral Neuropathy: A Paradigm Shift towards Brain-Centric Approaches

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(7), P. 659 - 659

Published: June 28, 2024

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment persist after remission. Whereas the latter situation disturbs quality life, life itself be endangered by appearance CIPN treatment. The causes have almost entirely been ascribed to neurotoxicity chemotherapeutic drugs in nervous system. However, central consequences are starting unraveled, namely supraspinal modulatory Based on our interests experience field, we undertook review brain-centered alterations underpin CIPN. changes descending modulation models along functional connectivity abnormalities brain patients analyzed. A translational analysis preclinical findings about regulation reviewed considering main neurochemical systems (serotoninergic noradrenergic) targeted management patients, antidepressants. In conclusion, this highlights importance studying areas involved understand pathophysiology CIPN, which will probably allow more personalized effective future.

Language: Английский

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Satellite glial contact enhances differentiation and maturation of human iPSC-derived sensory neurons

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Abstract Sensory neurons generated from induced pluripotent stem cells (iSNs) are used to model human peripheral neuropathies, however current differentiation protocols produce sensory with an embryonic phenotype. Peripheral glial contact early in development and contribute formation of the canonical pseudounipolar morphology, but these signals not encompassed iSN protocols. Here, we show that terminal iSNs co-culture rodent Dorsal Root Ganglion satellite glia (rSG) advances their maturation. Co-cultured develop a morphology through rSGs. This transition depends on semaphorin-plexin guidance cues gap junction signaling. In addition morphological changes, terminally differentiated exhibit enhanced spontaneous action potential firing, more mature gene expression, increased susceptibility paclitaxel axonal degeneration. Thus, coculture rSGs provide better for investigating neuropathies.

Language: Английский

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An Emerging Aspect of Cancer Neuroscience: A Literature Review on Chemotherapy-induced Peripheral Neuropathy

Cancer Letters, Journal Year: 2024, Volume and Issue: 611, P. 217433 - 217433

Published: Dec. 28, 2024

The nervous system governs both ontogeny and oncology. Foundational discoveries have clarified the direct communication of neurotransmitters with tumors indirect interactions through neural effects on immune tumor microenvironment. Meantime, is susceptible to cancer its treatment. Chemotherapy-induced peripheral neuropathy (CIPN) most common side that significantly reduce efficacy anti-cancer treatment patients' quality life by leading dose reduction or early cessation chemotherapy. However, there are no effective strategies reverse treat CIPN. A better understanding mechanisms expected enable development next generation therapies. Here, we summarize recent important studies clinical manifestations, risk factors, prediction, pathogenesis, prevention, We also provide perspectives insights regarding rationales bidirectional between system.

Language: Английский

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