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Medicine May 2021There are only a few studies that have shown an association of peripheral neuropathy with cognitive impairment in elderly individuals. Therefore, we investigated the... (Observational Study)
Observational Study
There are only a few studies that have shown an association of peripheral neuropathy with cognitive impairment in elderly individuals. Therefore, we investigated the relationship between cognitive performance and peripheral neuropathy.From the database of the National Health and Nutrition Examination Survey (NHANES, 1999-2002), each participant completed a household interview, physical performance test, questionnaire regarding personal health, and Digit Symbol Substitution Test (DSST) to evaluate cognitive performance. The severity of peripheral neuropathy was assessed based on the number of insensate areas in both feet during monofilament examination. We used the multivariate linear regression to analyze the association of the DSST findings with insensate areas of the worse foot.There were 828 participants in our study from NHANES 1999 to 2002; their mean age was 69.96 ± 7.38 years, and 51.3% were male. The β coefficients of the number of insensate areas associated with the DSST findings were all negative values, and the absolute value increased as the number of insensate areas increased. After adjustment for pertinent variables, the correlations remained significantly negative (all P for trend <.001). In addition, subgroup analysis showed no gender differences in the negative association, but this association was not significant in obese participants (P > .05).Our study provides evidence that the severity of peripheral neuropathy is significantly negatively correlated with cognitive performance.
Topics: Age Factors; Aged; Aged, 80 and over; Cognitive Dysfunction; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Nutrition Surveys; Peripheral Nervous System Diseases; Risk Factors; United States
PubMed: 34011128
DOI: 10.1097/MD.0000000000026071 -
International Journal of Molecular... Aug 2022(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral...
(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5−20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32−0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.
Topics: Animals; Antineoplastic Agents; Mice; Neoplasms; Omeprazole; Oxaliplatin; Peripheral Nervous System Diseases; Rats; Rodentia
PubMed: 36012136
DOI: 10.3390/ijms23168859 -
Molecular Pain 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting...
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting oncology patients' quality of life, chemotherapy-induced large-fiber (LF) neuropathy is amongst the least well understood components of CIPN, and one for which there is currently no established therapy. Preliminary clinical observations have led to the suggestion that Duloxetine, which is used for the treatment of pain associated with small-fiber CIPN (SF-CIPN), may be effective against LF-CIPN. In the present experiments we developed a model of LF-CIPN and studied the effect of Duloxetine on LF-CIPN induced by two neurotoxic chemotherapy agents: the proteasome inhibitor, Bortezomib, a first-line treatment of multiple myeloma; and, the anti-microtubule taxane, Paclitaxel, used in the treatment of solid tumors. Since there are currently no models for selective the study of LF-CIPN, our first aim was to establish a pre-clinical model in the rat. LF-CIPN was evaluated with the Current Perception Threshold (CPT) assay, which uses a high frequency (1000 Hz) electrical stimulus protocol that selectively activates large-fiber myelinated afferents. Our second aim was to use this model to test the hypothesis that Duloxetine can prevent LF-CIPN. We report that Bortezomib and Paclitaxel induce elevation of CPT, compatible with loss of large-fiber function, which are prevented by Duloxetine. Our findings support the clinical observation that Duloxetine may be an effective treatment for the large-fiber CIPN. We also suggest that CPT could be used as a biomarker for LF-CIPN in patients receiving neurotoxic chemotherapy.
Topics: Rats; Animals; Paclitaxel; Duloxetine Hydrochloride; Bortezomib; Rats, Sprague-Dawley; Quality of Life; Peripheral Nervous System Diseases; Antineoplastic Agents
PubMed: 37338165
DOI: 10.1177/17448069231185694 -
International Journal of Molecular... Aug 2021Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes... (Review)
Review
Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important.
Topics: Animals; Antineoplastic Agents, Phytogenic; Clinical Trials as Topic; Disease Models, Animal; Humans; Oxidative Stress; Paclitaxel; Peripheral Nervous System Diseases; Pre-Exposure Prophylaxis; Translational Research, Biomedical
PubMed: 34445439
DOI: 10.3390/ijms22168733 -
Oncology (Williston Park, N.Y.) Mar 2016
Topics: Antineoplastic Agents; Diagnosis, Differential; Diagnostic Techniques, Neurological; Electrodiagnosis; Humans; Medication Therapy Management; Neoplasms; Peripheral Nervous System Diseases
PubMed: 26984218
DOI: No ID Found -
Redox Biology 2014Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying... (Review)
Review
Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN) remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.
Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Biomarkers; Clinical Trials as Topic; Dietary Supplements; Humans; Mitochondria; Nerve Degeneration; Neuralgia; Neurons; Neuroprotective Agents; Oxidation-Reduction; Oxidative Stress; Peripheral Nervous System Diseases; Peroxynitrous Acid
PubMed: 24494204
DOI: 10.1016/j.redox.2014.01.006 -
Neurotherapeutics : the Journal of the... Mar 2023As cancer therapies advance and patient survival improves, there has been growing concern about the long-term adverse effects that patients may experience following... (Review)
Review
As cancer therapies advance and patient survival improves, there has been growing concern about the long-term adverse effects that patients may experience following treatment, and concerns have been raised about such persistent, progressive, and often irreversible adverse effects. Chemotherapy is a potentially life-extending treatment, and chemotherapy-induced peripheral neuropathy (CIPN) is one of its most common long-term toxicities. At present, strategies for the prevention and treatment of CIPN are still an open problem faced by medicine, and there has been a large amount of previous evidence that oxidative damage is involved in the process of CIPN. In this review, we focus on the lines of defense involving antioxidants that exert the effect of inhibiting CIPN. We also provide an update on the targets and clinical prospects of different antioxidants (melatonin, N-acetylcysteine, vitamins, α-lipoic acid, mineral elements, phytochemicals, nutritional antioxidants, cytoprotectants and synthetic compounds) in the treatment of CIPN with the help of preclinical and clinical studies, emphasizing the great potential of antioxidants as adjuvant strategies to mitigate CIPN.
Topics: Humans; Antineoplastic Agents; Antioxidants; Peripheral Nervous System Diseases; Acetylcysteine; Oxidative Stress
PubMed: 36735180
DOI: 10.1007/s13311-023-01346-8 -
Critical Reviews in Oncology/hematology May 2024Bortezomib is the first-line standard and most effective chemotherapeutic for multiple myeloma; however, bortezomib-induced peripheral neuropathy (BIPN) severely affects... (Review)
Review
Bortezomib is the first-line standard and most effective chemotherapeutic for multiple myeloma; however, bortezomib-induced peripheral neuropathy (BIPN) severely affects the chemotherapy regimen and has long-term impact on patients under maintenance therapy. The pathogenesis of BIPN is poorly understood, and basic research and development of BIPN management drugs are in early stages. Besides chemotherapy dose reduction and regimen modification, no recommended prevention and treatment approaches are available for BIPN apart from the International Myeloma Working Group guidelines for peripheral neuropathy in myeloma. An in-depth exploration of the pathogenesis of BIPN, development of additional therapeutic approaches, and identification of risk factors are needed. Optimizing effective and standardized BIPN treatment plans and providing more decision-making evidence for clinical diagnosis and treatment of BIPN are necessary. This article reviews the recent advances in BIPN research; provides an overview of clinical features, underlying molecular mechanisms, and therapeutic approaches; and highlights areas for future studies.
Topics: Humans; Bortezomib; Peripheral Nervous System Diseases; Antineoplastic Agents; Multiple Myeloma
PubMed: 38615869
DOI: 10.1016/j.critrevonc.2024.104353 -
International Journal of Molecular... Nov 2021Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with... (Review)
Review
Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody-antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.
Topics: Analgesics; Antibodies, Monoclonal; Gabapentin; Gangliosides; Humans; Morphine; Neoplasm Metastasis; Neuralgia; Neuroblastoma; Peripheral Nervous System Diseases
PubMed: 34884452
DOI: 10.3390/ijms222312648 -
Current Oncology (Toronto, Ont.) Aug 2021Although cancer and diabetes are common diseases, the relationship between diabetes, neuropathy and the risk of developing peripheral sensory neuropathy while or after... (Review)
Review
Although cancer and diabetes are common diseases, the relationship between diabetes, neuropathy and the risk of developing peripheral sensory neuropathy while or after receiving chemotherapy is uncertain. In this review, we highlight the effects of chemotherapy on the onset or progression of neuropathy in diabetic patients. We searched the literature in Medline and Scopus, covering all entries until 31 January 2021. The inclusion and exclusion criteria were: (1) original article (2) full text published in English or Spanish; (3) neuropathy was specifically assessed (4) the authors separately analyzed the outcomes in diabetic patients. A total of 259 papers were retrieved. Finally, eight articles fulfilled the criteria, and four more articles were retrieved from the references of the selected articles. The analysis of the studies covered the information about neuropathy recorded in 768 cancer patients with diabetes and 5247 control cases (non-diabetic patients). The drugs investigated are chemotherapy drugs with high potential to induce neuropathy, such as platinum derivatives and taxanes, which are currently the mainstay of treatment of various cancers. The predisposing effect of co-morbid diabetes on chemotherapy-induced peripheral neuropathy depends on the type of symptoms and drug used, but manifest at any drug regimen dosage, although greater neuropathic signs are also observed at higher dosages in diabetic patients. The deleterious effects of chemotherapy on diabetic patients seem to last longer, since peripheral neuropathy persisted in a higher proportion of diabetic patients than non-diabetic patients for up to two years after treatment. Future studies investigating the risk of developing peripheral neuropathy in cancer patients with comorbid diabetes need to consider the duration of diabetes, cancer-induced neuropathic effects per se (prior chemotherapy administration), and the effects of previous cancer management strategies such as radiotherapy and surgery.
Topics: Antineoplastic Agents; Diabetes Mellitus; Humans; Neoplasms; Peripheral Nervous System Diseases
PubMed: 34436039
DOI: 10.3390/curroncol28040273