Paclitaxel-induced neuropathic hypersensitivity in mice: Responses in 10 inbred mouse strains

Smith, Shad B.; Crager, Sara E.; Mogil, Jeffrey S.

doi:10.1016/j.lfs.2004.01.002

Cited by 128 publications

(115 citation statements)

References 24 publications

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“…We confirmed here that C57BL/6 mice do become hypersensitive to mechanical stimulation after intramuscular hypotonic saline injections, but apparently FVB mice do not. This is not as surprising as it may seem, because robust strain dependence of mechanical hypersensitivity has been demonstrated repeatedly (Mogil et al, 1999;Smith et al, 2004;LaCroix-Fralish et al, 2005). It should be noted that background genotype may also be influencing other discrepancies noted above, because the mutants in the study by Price et al (2001) were on an (129 ϫ C57BL/6)F 2 background, whereas the mutants in the study by Chen et al (2002) were on a (CD-1 ϫ C57BL/6)F 2 (or F 4 ) background.…”

Section: Asic Transgenic Mice Show Increased Sensitivity To Chemical/mentioning

confidence: 82%

Transgenic Expression of a Dominant-Negative ASIC3 Subunit Leads to Increased Sensitivity to Mechanical and Inflammatory Stimuli

Mogil

Breese²,

Witty³

et al. 2005

J. Neurosci.

114

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Molecular and behavioral evidence suggests that acid-sensing ion channels (ASICs) contribute to pain processing, but an understanding of their precise role remains elusive. Existing ASIC knock-out mouse experiments are complicated by the heteromultimerization of ASIC subunits. Therefore, we have generated transgenic mice that express a dominant-negative form of the ASIC3 subunit that inactivates all native neuronal ASIC-like currents by oligomerization. Using whole-cell patch-clamp recordings, we examined the response properties of acutely isolated dorsal root ganglion neurons to protons (pH 5.0). We found that whereas 33% of the proton-responsive neurons from wild-type mice exhibited an ASIC-like transient response, none of the neurons from the transgenic mice exhibited a transient inward current. Capsaicin-evoked responses mediated by the TRPV1 receptor were unaltered in transgenic mice. Adult male wild-type and transgenic mice were subjected to a battery of behavioral nociceptive assays, including tests of thermal, mechanical, chemical/inflammatory, and muscle pain. The two genotypes were equally sensitive to thermal pain and to thermal hypersensitivity after inflammation. Compared with wild types, however, transgenic mice were more sensitive to a number of modalities, including mechanical pain (von Frey test, tail-clip test), chemical/inflammatory pain (formalin test, 0.6% acetic acid writhing test), mechanical hypersensitivity after zymosan inflammation, and mechanical hypersensitivity after intramuscular injection of hypotonic saline. These data reinforce the hypothesis that ASICs are involved in both mechanical and inflammatory pain, although the increased sensitivity of transgenic mice renders it unlikely that they are direct transducers of nociceptive stimuli.

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Section: Asic Transgenic Mice Show Increased Sensitivity To Chemical/mentioning

confidence: 82%

Transgenic Expression of a Dominant-Negative ASIC3 Subunit Leads to Increased Sensitivity to Mechanical and Inflammatory Stimuli

Mogil

Breese²,

Witty³

et al. 2005

J. Neurosci.

114

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“…These models have been successfully used to evaluate potential therapeutic compounds [79,97,98]. An important concept that emerged from a unique study of paclitaxel CIPN in mice has been the dependency of the phenotype on the genetic background of the mice [99]. This study demonstrated that the various neuropathic pain outcome measures using the same dose of paclitaxel had different effects and did not result in any neuropathic behavior in some of the strains of mice.…”

Section: Chemotherapy-induced Peripheral Neuropathymentioning

confidence: 86%

Animal Models of Peripheral Neuropathies

Höke

2012

Neurotherapeutics

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Peripheral neuropathies are common neurological diseases, and various animal models have been developed to study disease pathogenesis and test potential therapeutic drugs. Three commonly studied disease models with huge public health impact are diabetic peripheral neuropathy, chemotherapy-induced peripheral neuropathy, and human immunodeficiency virus-associated sensory neuropathies. A common theme in these animal models is the comprehensive use of pathological, electrophysiological, and behavioral outcome measures that mimic the human disease.

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“…Several rodent models have been employed to investigate the symptoms and underlying mechanisms of paclitaxelinduced mechanical allodynia and thermal hyperalgesia [19][20][21] because paclitaxel-induced peripheral neuropathy in rats exhibits characteristics that are similar to those of human beings [22] . In the present animal model, paclitaxel induced rat hypersensitivity beginning on the 5th day after the first injection of paclitaxel, and interestingly, the mice exhibited neuropathic pain symptoms almost immediately after the injection.…”

Section: Discussionmentioning

confidence: 99%

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

et al. 2016

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Aim: Severe painful sensory neuropathy often occurs during paclitaxel chemotherapy. Since paclitaxel can activate mast cell and basophils, whereas quercetin, a polyphenolic flavonoid contained in various plants, which can specifically inhibit histamine release as a mast cell stabilizer. In this study we explore whether quercetin could ameliorate paclitaxel-induced neuropathic pain and elucidated the underlying mechanisms. Methods: Quercetin inhibition on histamine release was validated in vitro by detecting histamine release from rat basophilic leukemia (RBL-2H3) cells stimulated with paclitaxel (10 μmol/L). In the in vivo experiments, rats and mice received quercetin (20, 40 mg·kg -1 ·d -1 ) for 40 and 12 d, respectively. Meanwhile, the animals were injected with paclitaxel (2 mg/kg, ip) four times on d 1, 3, 5 and 7. Heat hyperalgesia and mechanical allodynia were evaluated at the different time points. The animals were euthanized and spinal cords and dorsal root ganglions were harvested for analyzing PKCε and TRPV1 expression levels. The plasma histamine levels were assessed in rats on d 31. Results: Pretreatment with quercetin (3, 10, 30 μmol/L) dose-dependently inhibited excessive histamine release from paclitaxelstimulated RBL-2H3 cells in vitro, and quercetin administration significantly suppressed the high plasma histamine levels in paclitaxeltreated rats. Quercetin administration dose-dependently raised the thresholds for heat hyperalgesia and mechanical allodynia in paclitaxel-treated rats and mice. Furthermore, quercetin administration dose-dependently suppressed the increased expression levels of PKCε and TRPV1 in the spinal cords and DRGs of paclitaxel-treated rats and mice. Moreover, quercetin administration may inhibited the translocation of PKCε from the cytoplasm to the membrane in the spinal cord and DRG of paclitaxel-treated rats. Conclusion: Our results reveal the underlying mechanisms of paclitaxel-induced peripheral neuropathy and demonstrate the therapeutic potential of quercetin for treating this side effect.

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Paclitaxel-induced neuropathic hypersensitivity in mice: Responses in 10 inbred mouse strains

Cited by 128 publications

References 24 publications

Transgenic Expression of a Dominant-Negative ASIC3 Subunit Leads to Increased Sensitivity to Mechanical and Inflammatory Stimuli

Transgenic Expression of a Dominant-Negative ASIC3 Subunit Leads to Increased Sensitivity to Mechanical and Inflammatory Stimuli

Animal Models of Peripheral Neuropathies

Quercetin ameliorates paclitaxel-induced neuropathic pain by stabilizing mast cells, and subsequently blocking PKCε-dependent activation of TRPV1

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