Paclitaxel-induced neuropathic pain is age dependent and devolves on glial response

Authors

  • J. Ruiz-Medina,

    1. Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
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  • A. Baulies,

    1. Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
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  • S.A. Bura,

    1. Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
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  • O. Valverde

    Corresponding author
    • Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
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  • Funding sources

    This work was supported by the Spanish Ministry of Science and Innovation (SAF 2010/15793), the Spanish Ministry of Health (PNSD 2010 and RTA 001/06/1001, FEDER) and the Generalitat de Catalunya (2009 SGR 684) to OV.

  • Conflict of interest

    The authors declare that there is no conflict of interest.

Correspondence

Olga Valverde

E-mail: olga.valverde@upf.edu

Abstract

Background

Paclitaxel is an antimitotic antitumour drug highly effective against a broad range of cancers considered refractory to conventional chemotherapy. One of the main serious side effects of paclitaxel treatment is the induction of peripheral neuropathic pain that often diminishes the patient's quality of life. In this study, we evaluated the severity of the neuropathy induced by paclitaxel and the inflammatory reaction in the dorsal horn of the spinal cord in young, adult and aged male CD1 mice.

Method

Hyperalgesia to noxious thermal stimulus and allodynia to non-noxious mechanical stimulus were evaluated using the plantar test and the von Frey filament model, respectively. Spinal cord microglia and astrocytes expression was assessed using Iba1 and glial fibrillary acidic protein immunofluorescence staining, respectively.

Results

All groups of mice showed a higher nociceptive reaction to thermal noxious (hyperalgesia) and mechanical non-noxious (allodynia) stimuli after paclitaxel treatment. However, these signs of neuropathy were enhanced in young mice followed by aged animals. Additionally, paclitaxel evoked a marked microglial and astrocytic response in the spinal cord of young and aged mice, whereas this enhanced reactivity was less important in adult mice. Indeed, the most severe glial activation observed in juvenile animals correlated well with major signs of neuropathy in this group of age.

Conclusion

Our results demonstrate that paclitaxel-induced neuropathy in mice is an age-dependent phenomenon whose severity devolves on glial response.

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