Docetaxel-induced peripheral neuropathy: Protective effects of dihydroprogesterone and progesterone in an experimental model

Ilaria Roglio, Roberto Bianchi, Francesca Camozzi, Valentina Carozzi, Ilaria Cervellini, Donatella Crippa, Giuseppe Lauria, Guido Cavaletti, Roberto C. Melcangi

Research output: Contribution to journalArticlepeer-review

Abstract

Peripheral neurotoxicity is a frequent complication limiting docetaxel chemotherapy in patients with cancer. We developed an experimental model that closely mimics the course of neuropathy in patients, aiming to investigate both the mechanisms of neurotoxicity at biochemical, functional and morphological levels and the potential neuroprotective role of neuroactive steroids. We demonstrated that treatment with dihydroprogesterone (DHP) or progesterone (P) counteracts docetaxel-induced neuropathy, preventing nerve conduction and thermal threshold changes, and degeneration of skin nerves in the foodpad. Neuroactive steroids also counteract the changes in gene expression of several myelin proteins and calcitonin gene-related peptide induced by docetaxel in sciatic nerve and lumbar spinal cord, respectively. Most nerve abnormalities observed during the treatment with docetaxel spontaneously recovered after drug withdrawal, similarly to what occurs in patients. However, results of midterm follow-up experiments indicated that animals cotreated with DHP or P have a faster recovery of the neuropathy compared with docetaxel-treated rats. Our study confirmed that neuroactive steroids exert a protective effect on peripheral nerves at different levels, suggesting that they might represent a new therapeutic frontier for patients with chemotherapy-induced neuropathy.

Original languageEnglish
Pages (from-to)36-44
Number of pages9
JournalJournal of the Peripheral Nervous System
Volume14
Issue number1
DOIs
Publication statusPublished - Mar 2009

Keywords

  • Myelin proteins
  • Neuroactive steroids
  • Neuroprotection
  • Neurotoxicity
  • Nociception

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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