Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel

Pandey, Praful; Kumar, Akash; Pushpam, Deepam; Khurana, Sachin; Malik, Prabhat Singh; Gogia, Ajay; Arunmozhimaran, Elavarasi; Singh, Mamta Bhushan; Chandran, Dinu S; Batra, Atul

doi:10.1186/s13063-023-07126-1

Cited by 3 publications

(1 citation statement)

References 15 publications

(17 reference statements)

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“…Clinical trials are undergoing to test the efficacy of gabapentin for pain relief in paclitaxel-induced CIPN patients. Preliminary results indicate a significant improvement in neurological outcomes (improved NCV and reversal of painful symptoms) in a small group of gabapentin-treated CIPN patients ( Aghili et al, 2019 ), despite the fact that the neuroprotective effect remains to be determined by using a larger cohort of patients ( Pandey et al, 2023 ).…”

Section: Molecular Mechanisms Underlying the Development Of Cipnmentioning

confidence: 99%

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy

Chen,

Gan,

et al. 2024

Front. Mol. Neurosci.

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Chemotherapy-induced peripheral neuropathy (CIPN) is the most common off-target adverse effects caused by various chemotherapeutic agents, such as cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib. CIPN is characterized by a substantial loss of primary afferent sensory axonal fibers leading to sensory disturbances in patients. An estimated of 19–85% of patients developed CIPN during the course of chemotherapy. The lack of preventive measures and limited treatment options often require a dose reduction or even early termination of life-saving chemotherapy, impacting treatment efficacy and patient survival. In this Review, we summarized the current understanding on the pathogenesis of CIPN. One prominent change induced by chemotherapeutic agents involves the disruption of neuronal cytoskeletal architecture and axonal transport dynamics largely influenced by the interference of microtubule stability in peripheral neurons. Due to an ineffective blood-nerve barrier in our peripheral nervous system, exposure to some chemotherapeutic agents causes mitochondrial swelling in peripheral nerves, which lead to the opening of mitochondrial permeability transition pore and cytochrome c release resulting in degeneration of primary afferent sensory fibers. The exacerbated nociceptive signaling and pain transmission in CIPN patients is often linked the increased neuronal excitability largely due to the elevated expression of various ion channels in the dorsal root ganglion neurons. Another important contributing factor of CIPN is the neuroinflammation caused by an increased infiltration of immune cells and production of inflammatory cytokines. In the central nervous system, chemotherapeutic agents also induce neuronal hyperexcitability in the spinal dorsal horn and anterior cingulate cortex leading to the development of central sensitization that causes CIPN. Emerging evidence suggests that the change in the composition and diversity of gut microbiota (dysbiosis) could have direct impact on the development and progression of CIPN. Collectively, all these aspects contribute to the pathogenesis of CIPN. Recent advances in RNA-sequencing offer solid platform for in silico drug screening which enable the identification of novel therapeutic agents or repurpose existing drugs to alleviate CIPN, holding immense promises for enhancing the quality of life for cancer patients who undergo chemotherapy and improve their overall treatment outcomes.

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Section: Molecular Mechanisms Underlying the Development Of Cipnmentioning

confidence: 99%

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy

Chen,

Gan,

et al. 2024

Front. Mol. Neurosci.

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Gabapentinoids for chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis

Chang,

Yang,

Liu

et al. 2024

BMJ Support Palliat Care

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IntroductionChemotherapy-induced peripheral neuropathy (CIPN) affects patients’ quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic.Materials/methodsWe searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events.ResultsFor the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) −0.14, 95% CI −0.51 to 0.23; I2=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI −4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD −0.28, 95% CI −0.57 to 0.01; I2=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies’ heterogeneity, a meta-analysis in treatment setting was not performed.ConclusionThere is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future.PROSPERO registration numberCRD42022361193.

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

Cunha,

Tavares,

Costa-Pereira

2024

Brain Sciences

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

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Randomized double-blind, placebo-controlled study of oral gabapentin for prevention of neuropathy in patients receiving paclitaxel

Cited by 3 publications

References 15 publications

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy

Gabapentinoids for chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis

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

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