Dysregulation of cellular calcium homeostasis in chemotherapy-evoked painful peripheral neuropathy

Anesth Analg. 2006 May;102(5):1485-90. doi: 10.1213/01.ane.0000204318.35194.ed.


Paclitaxel and vincristine are chemotherapeutic drugs that often evoke a long-lasting painful peripheral neuropathy. Using drugs that reduce intracellular or extracellular calcium ions (Ca2+), we investigated the hypothesis that impaired Ca2+ regulation contributes to the chemotherapy-evoked neuropathic pain syndrome. For comparison, we also tested rats with painful peripheral neuropathy caused by nerve trauma and to the anti-human immunodeficiency virus nucleoside analog 2',3'-dideoxycytidine (ddC). Normal naïve (without neuropathy), paclitaxel-treated, and vincristine-treated rats received the following intrathecal injections: TMB-8 (46 nmol), Quin-2 (1.8 nmol), EGTA (0.1 micromol), EGTA-am (0.1 micromol), and their vehicle controls. Chronic constriction injury (CCI) rats were examined after TMB-8 and Quin-2 injections, and ddC-treated rats were examined after receiving TMB-8. Mechano-allodynia and mechano-hyperalgesia were evaluated after each injection. Drug effects on heat hyperalgesia were also tested in CCI rats. All four Ca2+-reducing drugs significantly inhibited mechano-allodynia and mechano-hyperalgesia in the rats treated with paclitaxel, vincristine, or ddC, but no effects were seen in the CCI or naïve rats. We conclude that a similar abnormality of cellular Ca2+ homeostasis contributes to the pain caused by paclitaxel, vincristine, and ddC, but not posttraumatic painful peripheral neuropathy.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Calcium / metabolism*
  • Homeostasis / drug effects*
  • Homeostasis / physiology
  • Male
  • Pain / chemically induced
  • Pain / metabolism
  • Pain Measurement / drug effects*
  • Pain Measurement / statistics & numerical data
  • Peripheral Nervous System Diseases / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Antineoplastic Agents
  • Calcium