Methods and protocols for chemotherapy-induced peripheral neuropathy (CIPN) mouse models using paclitaxel

Pennypacker, Sarah D.; Fonseca, Miriam M.; Morgan, James W.; Dougherty, Patrick M.; Cubillos-Ruiz, Juan R.; Strowd, Roy; Romero‐Sandoval, E. Alfonso

doi:10.1016/bs.mcb.2021.12.019

Cited by 3 publications

(3 citation statements)

References 75 publications

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“…CIPN is a major complication of chemotherapies [108], such as paclitaxel (taxanes) and oxaliplatin [109]. Periodic intraperitoneal paclitaxel injections induced hind paw mechanical and thermal hypersensitivity [110]. CIPN is caused by glial cell activity and inflammatory cytokine and chemokine regulation [111].…”

Section: Chemotherapy-induced Peripheral Neuropathy (Cipn) Pain Modelmentioning

confidence: 99%

Role of Resolvins in Inflammatory and Neuropathic Pain

Park,

Roh,

Pan

et al. 2023

Pharmaceuticals

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Chronic pain is an unpleasant experience associated with actual or potential tissue damage. Inflammatory pain alerts the body to inflammation and promotes healing; however, unresolved inflammation can lead to chronic pain. Conversely, neuropathic pain, due to somatosensory damage, can be a disease in itself. However, inflammation plays a considerable role in the progression of both types of pain. Resolvins, derived from omega-3 fatty acids, actively suppress pro-inflammatory mediators and aid in the resolution of inflammation. Resolvins alleviate various inflammatory and neuropathic pain models by reducing hypersensitivity and regulating inflammatory cytokines and glial activation in the spinal cord and dorsal root ganglia. Thus, resolvins are a promising alternative for pain management with the potential to reduce the side effects associated with conventional medications. Continued research is crucial to unlock the therapeutic potential of resolvins and integrate them into effective clinical pain management strategies. This review aimed to evaluate the literature surrounding the resolvins in inflammatory and neuropathic pain.

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Section: Chemotherapy-induced Peripheral Neuropathy (Cipn) Pain Modelmentioning

confidence: 99%

Role of Resolvins in Inflammatory and Neuropathic Pain

Park,

Roh,

Pan

et al. 2023

Pharmaceuticals

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“…The removal of genetic variability minimizes phenotypic or trait variability, thereby enhancing the reproducibility of the model [ 7 ]. In the majority of TIPN experiments, the age of the mice ranged from four weeks up to adulthood [ 8 ] and TIPN was induced by cumulative doses of Taxol ranging from 4 mg/kg up to 180 mg/kg, delivered in the majority of preclinical studies by the intraperitoneal (i.p.) route of administration, causing a significant peripheral polyneuropathy in 91% of the experiments using males [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, the results with mice TIPN models treated with Taxol show high efficacy in causing TIPN (also across sex and various strains used) [ 6 ], and this is in line with the findings that Taxol is a chemotherapeutic drug causing one of the highest TIPN rates in patients [ 10 ]. With this background, in the present study, we generated the TIPN model in young C57BL/6J male mice by injection of Taxol (6 mg/kg), administered i.p., once daily, for a total of eight injections, to a cumulative intermittent low-dose of 48 mg/kg, to induce prolonged mechanical hypersensitivity and thermal hypoalgesia, mimicking one cycle of chemotherapy treatment in cancer patients [ 8 ]. Theoretically, it is preferable to use animal models that replicate all symptoms observed in humans.…”

Section: Introductionmentioning

confidence: 99%

Gabapentin Increases Intra-Epidermal and Peptidergic Nerve Fibers Density and Alleviates Allodynia and Thermal Hyperalgesia in a Mouse Model of Acute Taxol-Induced Peripheral Neuropathy

Klazas

Naamneh

Zheng³

et al. 2022

Biomedicines

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The clinical pathology of Taxol-induced peripheral neuropathy (TIPN), characterized by loss of sensory sensitivity and pain, is mirrored in a preclinical pharmacological mice model in which Gabapentin, produced anti-thermal hyperalgesia and anti-allodynia effects. The study aimed to investigate the hypothesis that gabapentin may protect against Taxol-induced neuropathic pain in association with an effect on intra-epidermal nerve fibers density in the TIPN mice model. A TIPN study schedule was induced in mice by daily injection of Taxol during the first week of the experiment. Gabapentin therapy was performed during the 2nd and 3rd weeks. The neuropathic pain was evaluated during the whole experiment by the Von Frey, tail flick, and hot plate tests. Intra-epidermal nerve fibers (IENF) density in skin biopsies was measured at the end of the experiment by immunohistochemistry of ubiquitin carboxyl-terminal hydrolase PGP9.5 pan-neuronal and calcitonin gene-related (CGRP) peptides-I/II- peptidergic markers. Taxol-induced neuropathy was expressed by 80% and 73% reduction in the paw density of IENFs and CGPR, and gabapentin treatment corrected by 83% and 46% this reduction, respectively. Gabapentin-induced increase in the IENF and CGRP nerve fibers density, thus proposing these evaluations as an additional objective end-point tool in TIPN model studies using gabapentin as a reference compound.

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Translation of paclitaxel-induced peripheral neurotoxicity from mice to patients: the importance of model selection

Cavaletti,

Alberti,

Canta

et al. 2024

Pain

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Paclitaxel-induced peripheral neurotoxicity (PIPN) is a potentially dose-limiting side effect in anticancer chemotherapy. Several animal models of PIPN exist, but their results are sometimes difficult to be translated into the clinical setting. We compared 2 widely used PIPN models characterized by marked differences in their methodologies. Female C57BL/6JOlaHsd mice were used, and they received only paclitaxel vehicle (n = 38) or paclitaxel via intravenous injection (n = 19, 70 mg/kg) once a week for 4 weeks (Study 1) or intraperitoneally (n = 19, 10 mg/kg) every 2 days for 7 times (Study 2). At the end of treatment and in the follow-up, mice underwent behavioral and neurophysiological assessments of PIPN. At the same time points, some mice were killed and dorsal root ganglia, skin, and sciatic and caudal nerve samples underwent pathological examination. Serum neurofilament light levels were also measured. The differences in the neurotoxicity parameters were analyzed using a nonparametric Mann-Whitney test, with significance level set at P < 0.05. Study 1 showed significant and consistent behavioral, neurophysiological, pathological, and serological changes induced by paclitaxel administration at the end of treatment, and most of these changes were still evident in the follow-up period. By contrast, study 2 evidenced only a transient small fiber neuropathy, associated with neuropathic pain. Our comparative study clearly distinguished a PIPN model recapitulating all the clinical features of the human condition and a model showing only small fiber neuropathy with neuropathic pain induced by paclitaxel.

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Methods and protocols for chemotherapy-induced peripheral neuropathy (CIPN) mouse models using paclitaxel

Cited by 3 publications

References 75 publications

Role of Resolvins in Inflammatory and Neuropathic Pain

Role of Resolvins in Inflammatory and Neuropathic Pain

Gabapentin Increases Intra-Epidermal and Peptidergic Nerve Fibers Density and Alleviates Allodynia and Thermal Hyperalgesia in a Mouse Model of Acute Taxol-Induced Peripheral Neuropathy

Translation of paclitaxel-induced peripheral neurotoxicity from mice to patients: the importance of model selection

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