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 Google Scholar Articles by Sugimoto, K. Articles by Strichartz, G. PubMed PubMed Citation Articles by Sugimoto, K. Articles by Strichartz, G. Related Collections Mechanisms Pain Mechanisms Pain Pharmacology

---

PAIN MECHANISMS

A High Concentration of Resiniferatoxin Inhibits Ion Channel Function in Clonal Neuroendocrine Cells

From the Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Address correspondence and reprint requests to G. Strichartz, PhD, MRB 613/BWH, 75 Francis St., Boston, MA 02115-6110. Address e-mail to gstrichz{at}zeus.bwh.harvard.edu.

Abstract

BACKGROUND: Resiniferatoxin (RTX) is a potent agonist of the transient receptor potential vanilloid 1 channel (TRPV1) found in peripheral nociceptors. RTX causes cellular excitation first, followed by a long-lasting refractory state, which has suggested its therapeutic use for pain control. RTX's effect could result from specific actions on TRPV1 channels, but might also arise from previously reported TRPV1-independent effects. We have tested whether exposure to RTX compromises ion channels in a TRPV1-independent manner.

METHODS: Clonal rat anterior pituitary (GH₃) cells, loaded with the Ca⁺²-sensitive fluorescent dye (fluo-4), were stimulated with the Na⁺ channel activator veratridine (VTD) or directly depolarized by 60 mM K⁺ solution. The physiological effects of exposure to RTX were evaluated by stimulated increases of fluorescence from raised intracellular [Ca²⁺].

RESULTS: The presence of 10 µM RTX acutely reduced the median fluorescence changes by VTD and 60 mM K⁺ to 45% and 50%, respectively (P = 0.018 and 0.043). Prolonged exposure (24 h) of cells to 10 µM RTX, followed by a 2 h washout, reduced the median fluorescence changes by VTD and 60 mM K⁺ to 5.6% and 42% of control changes, respectively (P = 0.027 and 0.011). Cell responses to VTD partially recovered, to 42% of control, after incubation in RTX-free medium for 24 h.

CONCLUSION: RTX at 10 µM directly and acutely inhibited voltage-dependent Ca²⁺ channels, in a TRPV1-independent manner. Prolonged exposure (24 h) to 10 µM RTX inhibited voltage-dependent Na⁺ channels in addition to the Ca²⁺ channels, in at least a partially reversible manner.

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