Prevention and treatment of chemotherapy-induced peripheral neuropathy

Piccolo, Jennifer K; Kolesar, Jill M.

doi:10.2146/ajhp130126

Cited by 81 publications

(56 citation statements)

References 29 publications

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“…Unfortunately, however, conventional symptomatic management of neuropathic pain such as nortriptyline, amitriptyline, gabapentin, and lamotrigine failed to improve neuropathic patients in placebo-controlled, double-blinded clinical trials [16]. Ca/Mg infusion and venlafaxine, a serotonin-norepinephrine reuptake inhibitor, are known to be effective in preventing OXIPN; however, they are not routinely used because of concerns related with decreased chemotherapy efficacies [43]. Based on the mechanisms underlying the development of OXIPN, several preclinical studies reported some promising agents that exhibited neuroprotection against OXIPN.…”

Section: Discussionmentioning

confidence: 99%

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Cho

Park

et al. 2016

BMC Complement Altern Med

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BackgroundOxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients. Until now, no effective preventive or therapeutic drug has been developed; therefore, the dose-limiting factor of OXIPN is still an obstacle in the use of oxaliplatin to treat cancer patients. In the present study, we report for the first time that the aqueous extract of Lithospermi radix (WLR) can attenuate the OXIPN in both in vitro and in vivo neuropathic models.MethodsThe protective effect of WLR on OXIPN was evaluated in vitro by quantifying nerve growth factor (NGF)-stimulated neurite outgrowth in PC12 cells treated with a combination of oxaliplatin and WLR. The neuroprotective potential of WLR was further confirmed by measuring the changes in nociceptive sensitivities to external mechanical stimuli in neuropathic animals induced by oxaliplatin. Histological and immunohistochemical studies were further done to examine the effect of WLR in mouse spinal cords and footpads.ResultsOxaliplatin-induced neurotoxicity in NGF-stimulated PC12 cells. It could reduce the lengths and branching numbers of neuritis in NGF-stimulated PC12 cells. Co-treatment of WLR rescued the differentiated PC12 cells from the neurotoxicity of oxaliplatin. In a chronic OXIPN animal model, administration of oxaliplatin i.p. induced enhanced nociceptive sensitivity to mechanical stimuli (25.0 to 72.5 % of response rate) along with spinal activation of microglias and astrocytes and loss of intraepidermal nerve fibers in footpads, which is remarkably suppressed by oral administration of WLR (67.5 to 35 % of response rate at the end of experiment). Cytotoxicity of oxaliplatin determined in human cancer cells was not affected irrespective of the presence of WLR.ConclusionsIn conclusion, we demonstrated that WLR can attenuate OXIPN in both in vitro and in vivo experimental models, which may be in part attributed to its anti-inflammatory activity in the spinal cord and its neuroprotective potential in the peripheral nerve system without affecting the anti-tumor potential of oxaliplatin. Therefore, WLR could be considered as a good starting material to develop a novel therapeutic agent targeting OXIPN. However, further studies should be done to elucidate the underlying mechanism such as molecular targets and active constituent(s) in WLR with neuroprotective potential.

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Section: Discussionmentioning

confidence: 99%

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Cho

Park

et al. 2016

BMC Complement Altern Med

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“…In fact, oxaliplatin can cause both acute neuropathy (transient, distal paresthesia during or shortly after the first minutes of infusion) and chronic sensory neuropathy (distal paresthesia and numbness which can lead to functional disability, in the case of grade 3 toxicity). These neurosensory symptoms increase in intensity with cumulative doses, persist between cycles and affect the quality of life in the majority of patients (Coriat et al, 2014;Piccolo & Kolesar, 2014).…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer

et al. 2014

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The purpose of this study was to evaluate both in vitro and in vivo anticancer activities against colorectal cancer (CRC) of electrospun polylactide (PLA) nanofibers loaded with 5-fluorouracil (5-Flu) and oxaliplatin. For in vitro evaluation, human CRC HCT8 cells were directly exposed to the drug-loaded fiber mats, followed with MTT and flow cytometry (FCM) assay. For in vivo evaluation, the drug-loaded fiber mats were locally implanted into mouse colorectal CT26 tumor-bearing mice, followed with histological analysis and detection of survival rate. The results showed that the drug-loaded fiber mats was similar to that of the combination of free 5-Flu and oxaliplatin in vitro cytotoxicity but was much superior to intravenous injection of free drug in vivo anticancer activities, presenting with suppressed tumor growth rate and prolonged survival time of mice. In conclusion, anticancer activities of 5-Flu and oxaliplatin against CRC can be significantly improved by using PLA electrospun nanofibers as local drug delivery system.

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“…Another potential explanation for this finding may be that the observed effect of high doses of pregabalin on cold allodynia involves an additional molecular target or putative mechanism. The previously observed in mouse models weak efficacy of pregabalin in reducing cold allodynia is parallel to clinical findings, that is, despite benefits seen in smaller trials, a Phase IV study conducted to assess the efficacy of interventional pregabalin in treatment of CIPN was terminated early due to insufficient antiallodynic efficacy of this drug (Piccolo & Kolesar, 2014).…”

Section: Discussionmentioning

confidence: 87%

Searching for analgesic drug candidates alleviating oxaliplatin‐induced cold hypersensitivity in mice

2019

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Oxaliplatin is a third‐generation, platinum‐based derivative used to treat advanced colorectal cancer. Within the patient population on oxaliplatin therapy, a lower incidence of hematological adverse effects and gastrointestinal toxicity is noted, but severe neuropathic pain episodes characterized by increased cold and tactile hypersensitivity are present in ~95% of patients. This drug is also used to induce a rodent model of chemotherapy‐induced peripheral neuropathy (CIPN)‐related neuropathic pain which is widely used in the search for novel therapies for CIPN prevention and treatment. This paper provides a step‐by‐step, detailed description of the prevention and intervention protocols used in our laboratory for the assessment of oxaliplatin‐induced cold allodynia in mice. To establish cold sensitivity in mice, the cold plate test was used. Latencies to pain reaction in response to cold stimulus (2.5°C) for vehicle‐treated non‐neuropathic mice, vehicle‐treated mice injected with oxaliplatin (neuropathic control), and oxaliplatin‐treated mice treated additionally with duloxetine are compared. Duloxetine is a serotonin/noradrenaline reuptake inhibitor which was found to produce significant pain relief in patients with CIPN symptoms. In our present study, duloxetine administered intraperitoneally at the dose of 30 mg/kg served as a model antiallodynic drug which attenuated or partially prevented cold allodynia caused by oxaliplatin.

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Prevention and treatment of chemotherapy-induced peripheral neuropathy

Cited by 81 publications

References 29 publications

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Aqueous extract of Lithospermi radix attenuates oxaliplatin-induced neurotoxicity in both in vitro and in vivo models

Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer

Searching for analgesic drug candidates alleviating oxaliplatin‐induced cold hypersensitivity in mice

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