HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 100/4/2300    most recent 01337.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Hamamoto, D. T. Articles by Simone, D. A. PubMed PubMed Citation Articles by Hamamoto, D. T. Articles by Simone, D. A.

Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin

Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, Minnesota

Submitted 7 July 2008; accepted in final form 31 July 2008

Primary and metastatic cancers that effect bone are frequently associated with pain. Sensitization of primary afferent C nociceptors innervating tissue near the tumor likely contributes to the chronic pain and hyperalgesia accompanying this condition. This study focused on the role of the endogenous peptide endothelin-1 (ET-1) as a potential peripheral algogen implicated in the process of cancer pain. Electrophysiological response properties, including ongoing activity and responses evoked by heat stimuli, of C nociceptors were recorded in vivo from the tibial nerve in anesthetized control mice and mice exhibiting mechanical hyperalgesia following implantation of fibrosarcoma cells into and around the calcaneus bone. ET-1 (100 µM) injected into the receptive fields of C nociceptors innervating the plantar surface of the hind paw evoked an increase in ongoing activity in both control and tumor-bearing mice. Moreover, the selective ET_A receptor antagonist, BQ-123 (3 mM), attenuated tumor-evoked ongoing activity in tumor-bearing mice. Whereas ET-1 produced sensitization of C nociceptors to heat stimuli in control mice, C nociceptors in tumor-bearing mice were sensitized to heat, and their responses were not further increased by ET-1. Importantly, administration of BQ-123 attenuated tumor-evoked sensitization of C nociceptors to heat. We conclude that ET-1 at the tumor site contributes to tumor-evoked excitation and sensitization of C nociceptors through an ET_A receptor mediated mechanism.