Paclitaxel-induced neuropathic pain is age dependent and devolves on glial response
Article first published online: 24 MAY 2012
© 2012 European Federation of International Association for the Study of Pain Chapters
European Journal of Pain
Volume 17, Issue 1, pages 75–85, January 2013
How to Cite
Ruiz-Medina, J., Baulies, A., Bura, S.A. and Valverde, O. (2013), Paclitaxel-induced neuropathic pain is age dependent and devolves on glial response. European Journal of Pain, 17: 75–85. doi: 10.1002/j.1532-2149.2012.00172.x
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.
- Issue published online: 11 DEC 2012
- Article first published online: 24 MAY 2012
- Manuscript Accepted: 30 APR 2012
- Spanish Ministry of Science and Innovation. Grant Number: SAF 2010/15793
- Spanish Ministry of Health. Grant Numbers: PNSD 2010, RTA 001/06/1001, FEDER
- Generalitat de Catalunya. Grant Number: 2009 SGR 684
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.
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.
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.
Our results demonstrate that paclitaxel-induced neuropathy in mice is an age-dependent phenomenon whose severity devolves on glial response.