Dysregulation of cellular calcium homeostasis in chemotherapy-evoked painful peripheral neuropathy.
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.
Siau
Chiang
C
Department of Anesthesia, McGill University, Montreal, Quebec, Canada.
Bennett
Gary J
GJ
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects* / Q000706:statistics & numerical data; D010523:Peripheral Nervous System Diseases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D002118:Calcium