European Journal of Cancer
Volume 45, Issue 1 , Pages 154-163, January 2009

Neurotropin reverses paclitaxel-induced neuropathy without affecting anti-tumour efficacy

  • Takehiro Kawashiri

      Affiliations

    • Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • ,
  • Nobuaki Egashira

      Affiliations

    • Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
    • Corresponding Author InformationCorresponding author: Tel.: +81 92 642 5920; fax: +81 92 642 5937.
  • ,
  • Yoshinori Itoh

      Affiliations

    • Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan
  • ,
  • Takao Shimazoe

      Affiliations

    • Department of Pharmacoepidemiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • ,
  • Yoko Ikegami

      Affiliations

    • Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • ,
  • Takahisa Yano

      Affiliations

    • Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
  • ,
  • Megumu Yoshimura

      Affiliations

    • Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • ,
  • Ryozo Oishi

      Affiliations

    • Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

Received 2 May 2008; received in revised form 26 September 2008; accepted 6 October 2008. published online 25 November 2008.

Abstract 

Paclitaxel is a commonly used anticancer drug, but it frequently causes peripheral neuropathy. Neurotropin, a non-protein extract from inflamed rabbit skin inoculated with vaccinia virus, has been used to treat various chronic painful conditions. In the present study, we investigated the effect of neurotropin on the paclitaxel-induced neuropathy in rats. Repeated administration of paclitaxel induced mechanical allodynia, cold hyperalgesia, and motor dysfunction. These neuropathies were mostly reversed by the repeated administration of neurotropin. Furthermore, neurotropin ameliorated the paclitaxel-induced axonal degeneration in cultured PC12 and rat dorsal root ganglion cells, and in rat sciatic nerve. In addition, neurotropin did not affect the microtubule aggregation or anti-tumour effect induced by paclitaxel in the tumour cell lines or tumour cells-implanted mice. These results suggest that neurotropin reverses the paclitaxel-induced neuropathy without affecting anti-tumour activity of paclitaxel, and therefore may be useful for the paclitaxel-induced neuropathy in clinical settings.

Keywords: Neurotropin, Paclitaxel, Neuropathy, Allodynia, Neurite outgrowth, Anti-tumour activity

 

PII: S0959-8049(08)00803-4

doi:10.1016/j.ejca.2008.10.004

European Journal of Cancer
Volume 45, Issue 1 , Pages 154-163, January 2009