Mini-Review: Mitochondrial dysfunction and chemotherapy-induced neuropathic pain

Doyle, Tim; Salvemini, Daniela

doi:10.1016/j.neulet.2021.136087

Cited by 45 publications

(35 citation statements)

References 104 publications

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“…Duloxetine has been recommended for the treatment of established CIPN but lacks the support of mechanistic evidence with limited beneficial outcome [ 18 , 19 ]. Preclinical studies are examining the role of neuronal ion transport channels, mitochondrial function, oxidative stress, and inflammation to develop novel approaches to ameliorate CIPN [ 18 , 19 , 20 , 21 ]. Oxidative stress appears to be central in mediating the therapeutic effect of chemotherapy in cancer.…”

Section: Chemotherapy Induces Peripheral Neuropathymentioning

confidence: 99%

Endoplasmic Reticulum Stress in Chemotherapy-Induced Peripheral Neuropathy: Emerging Role of Phytochemicals

2022

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Chemotherapy-induced peripheral neuropathy (CIPN) is a significant dose-limiting long-term sequela in cancer patients undergoing treatment, often leading to discontinuation of treatment. No established therapy exists to prevent and/or ameliorate CIPN. Reactive oxygen species (ROS) and mitochondrial dysregulation have been proposed to underlie the pathobiology of CIPN. However, interventions to prevent and treat CIPN are largely ineffective. Additional factors and mechanism-based targets need to be identified to develop novel strategies to target CIPN. The role of oxidative stress appears to be central, but the contribution of endoplasmic reticulum (ER) stress remains under-examined in the pathobiology of CIPN. This review describes the significance of ER stress and its contribution to CIPN, the protective role of herbal agents in countering ER stress in nervous system-associated disorders, and their possible repurposing for preventing CIPN.

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Section: Chemotherapy Induces Peripheral Neuropathymentioning

confidence: 99%

Endoplasmic Reticulum Stress in Chemotherapy-Induced Peripheral Neuropathy: Emerging Role of Phytochemicals

2022

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“…Maintaining mitochondrial function has been proposed as a possible treatment technique for treating or preventing chronic pain [80]. For example, strategies that improve mitochondrial function have shown success in preventing and reversing CIPN in pre-clinical animal models and have begun to show some progress toward translation to the clinic [81]. Although dietary intake ultimately directs metabolism, only a few studies showed how metabolic pathways influenced by diet may have a role in the immune activation seen in chronic pain [82].…”

Section: Impact Of Diet and Nutrition On Pain In Cancer Survivors Through The Immune System And Systemic Inflammationmentioning

confidence: 99%

Diet/Nutrition: Ready to Transition from a Cancer Recurrence/Prevention Strategy to a Chronic Pain Management Modality for Cancer Survivors?

Yılmaz

Malfliet

Elma

et al. 2022

JCM

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Evidence for the relationship between chronic pain and nutrition is mounting, and chronic pain following cancer is gaining recognition as a significant area for improving health care in the cancer survivorship population. This review explains why nutrition should be considered to be an important component in chronic pain management in cancer survivors by exploring relevant evidence from the literature and how to translate this knowledge into clinical practice. This review was built on relevant evidence from both human and pre-clinical studies identified in PubMed, Web of Science and Embase databases. Given the relationship between chronic pain, inflammation, and metabolism found in the literature, it is advised to look for a strategic dietary intervention in cancer survivors. Dietary interventions may result in weight loss, a healthy body weight, good diet quality, systemic inflammation, and immune system regulations, and a healthy gut microbiota environment, all of which may alter the pain-related pathways and mechanisms. In addition to being a cancer recurrence or prevention strategy, nutrition may become a chronic pain management modality for cancer survivors. Although additional research is needed before implementing nutrition as an evidence-based management modality for chronic pain in cancer survivors, it is already critical to counsel and inform this patient population about the importance of a healthy diet based on the data available so far.

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“…Under neuropathic pain conditions, the mitochondrial CA VA and CA VB isoforms are of particular interest. It has been shown that mitochondrial CA VA/VB regulate the respiration rate as well as reactive oxygen species (ROS) production, oxidative stress, and apoptosis [ 21 ], and mitochondrial dysfunction is implicated in chemotherapy-induced neuropathic pain [ 22 ]. Indeed, mitochondria are involved in many essential functions, including ATP production through oxidative phosphorylation, apoptosis regulation, intracellular calcium homeostasis, and ROS production.…”

Section: Introductionmentioning

confidence: 99%

“…Many factors are involved in the maintenance of mitochondrial activity, and during the last decade, a large body of evidence indicates that chemotherapeutic drugs determine mitochondrial injury characterized by loss of mitochondrial morphology and disruption of oxidative phosphorylation and mitochondrial membrane potential. All of these events determine a reduction in ATP production and increase of the reliance on glycolysis, causing a decrease in the cellular bio-energetic capacity [ 22 ]. Moreover, an uncontrolled release of ROS and reactive nitrogen species (RNS) evoked by antioxidant enzyme deregulation may cause oxidative stress and nitrosylative and nitrative reactions with proteins and nucleic acids, and these phenomena can be strongly involved in the onset of neuropathic pain induced by chemotherapy [ 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Micheli

Testai

Angeli

et al. 2022

IJMS

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Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca2+ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs.

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Mini-Review: Mitochondrial dysfunction and chemotherapy-induced neuropathic pain

Cited by 45 publications

References 104 publications

Endoplasmic Reticulum Stress in Chemotherapy-Induced Peripheral Neuropathy: Emerging Role of Phytochemicals

Endoplasmic Reticulum Stress in Chemotherapy-Induced Peripheral Neuropathy: Emerging Role of Phytochemicals

Diet/Nutrition: Ready to Transition from a Cancer Recurrence/Prevention Strategy to a Chronic Pain Management Modality for Cancer Survivors?

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

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