Tumor-evoked sensitization of C nociceptors: a role for endothelin.

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 microM) 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.

• Authors: Darryl T Hamamoto, Sergey G Khasabov, David M Cain, Donald A Simone
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 100 Issue 4 Pg. 2300-11 (Oct 2008) ISSN: 0022-3077 [Print] United States
• PMID: 18684911 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin A Receptor Antagonists
• Endothelins
• Peptides, Cyclic
• cyclo(Trp-Asp-Pro-Val-Leu)

Topics

• Animals
• Behavior, Animal (physiology)
• Cell Line, Tumor
• Electrophysiology
• Endothelin A Receptor Antagonists
• Endothelins (metabolism, physiology)
• Fibrosarcoma (pathology)
• Hot Temperature
• Hyperalgesia (etiology, metabolism, physiopathology)
• Male
• Mice
• Mice, Inbred C3H
• Neoplasm Transplantation
• Neoplasms (complications, metabolism)
• Nerve Fibers, Unmyelinated (physiology)
• Neural Conduction (physiology)
• Neurons, Afferent (metabolism, physiology)
• Nociceptors (physiology)
• Peptides, Cyclic (pharmacology)
• Peripheral Nervous System Diseases (physiopathology, psychology)