Tumor-evoked sensitization of C nociceptors

A role for endothelin

Darryl T. Hamamoto, Sergey Khasabov, David M. Cain, Donald A Simone

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 ETA 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 ETA receptor mediated mechanism.

Original languageEnglish (US)
Pages (from-to)2300-2311
Number of pages12
JournalJournal of neurophysiology
Volume100
Issue number4
DOIs
StatePublished - Oct 1 2008

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Nociceptors
Endothelins
Endothelin-1
Neoplasms
Hot Temperature
Hyperalgesia
Bone Neoplasms
Calcaneus
Tibial Nerve
Fibrosarcoma
Chronic Pain
Bone and Bones
Pain
Peptides

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Tumor-evoked sensitization of C nociceptors : A role for endothelin. / Hamamoto, Darryl T.; Khasabov, Sergey; Cain, David M.; Simone, Donald A.

In: Journal of neurophysiology, Vol. 100, No. 4, 01.10.2008, p. 2300-2311.

Research output: Contribution to journalArticle

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