JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siau, C. Articles by Bennett, G. J. Search for Related Content PubMed PubMed Citation Articles by Siau, C. Articles by Bennett, G. J. Related Collections Mechanisms Pain

---

PAIN MEDICINE

Dysregulation of Cellular Calcium Homeostasis in Chemotherapy-Evoked Painful Peripheral Neuropathy

Chiang Siau, MMED(Anaesth)^*, and Gary J. Bennett, PhD^*

Departments of *Anesthesia and Dentistry and Centre for Research on Pain, McGill University, Montreal, Quebec, Canada

Address correspondence and reprint requests to Gary J. Bennett, PhD, Anesthesia Research Unit, McGill University, 3655 Promenade Sir William Osler (McIntyre 1202), Montreal, Quebec, Canada H3G 1Y6. Address e-mail to gary.bennett{at}mcgill.ca.

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 µmol), EGTA-am (0.1 µmol), 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.

This article has been cited by other articles:

				E. J. Rahn, A. M. Zvonok, G. A. Thakur, A. D. Khanolkar, A. Makriyannis, and A. G. Hohmann Selective Activation of Cannabinoid CB2 Receptors Suppresses Neuropathic Nociception Induced by Treatment with the Chemotherapeutic Agent Paclitaxel in Rats J. Pharmacol. Exp. Ther., November 1, 2008; 327(2): 584 - 591. [Abstract] [Full Text] [PDF]

				T. Bordet, B. Buisson, M. Michaud, J.-L. Abitbol, F. Marchand, J. Grist, E. Andriambeloson, M. Malcangio, and R. M. Pruss Specific Antinociceptive Activity of Cholest-4-en-3-one, Oxime (TRO19622) in Experimental Models of Painful Diabetic and Chemotherapy-Induced Neuropathy J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 623 - 632. [Abstract] [Full Text] [PDF]

				W. Boehmerle, K. Zhang, M. Sivula, F. M. Heidrich, Y. Lee, S.-E. Jordt, and B. E. Ehrlich Chronic exposure to paclitaxel diminishes phosphoinositide signaling by calpain-mediated neuronal calcium sensor-1 degradation PNAS, June 26, 2007; 104(26): 11103 - 11108. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999