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

  • J. Ruiz‐Medina
    Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut Universitat Pompeu Fabra Barcelona Spain
  • A. Baulies
    Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut Universitat Pompeu Fabra Barcelona Spain
  • S.A. Bura
    Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut Universitat Pompeu Fabra Barcelona Spain
  • O. Valverde
    Grup de Recerca en Neurobiologia del Comportament (GReNeC), Departament de Ciències Experimentals i de la Salut Universitat Pompeu Fabra Barcelona Spain

説明

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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 <jats:styled-content style="fixed-case">CD</jats:styled-content>1 mice.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>Hyperalgesia to noxious thermal stimulus and allodynia to non‐noxious mechanical stimulus were evaluated using the plantar test and the <jats:styled-content style="fixed-case">v</jats:styled-content>on <jats:styled-content style="fixed-case">F</jats:styled-content>rey filament model, respectively. Spinal cord microglia and astrocytes expression was assessed using <jats:styled-content style="fixed-case">I</jats:styled-content>ba1 and glial fibrillary acidic protein immunofluorescence staining, respectively.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our results demonstrate that paclitaxel‐induced neuropathy in mice is an age‐dependent phenomenon whose severity devolves on glial response.</jats:p></jats:sec>

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