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Tumor-evoked sensitization of C nociceptors: a role for endothelin.
J Neurophysiol. 2008 Oct; 100(4):2300-11.JN

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+Show Affiliations

Department of Diagnostic and Biological Sciences, University of Minnesota, 515 Delaware St. SE, 17-252 Moos Tower, Minneapolis, MN 55455, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18684911

Citation

Hamamoto, Darryl T., et al. "Tumor-evoked Sensitization of C Nociceptors: a Role for Endothelin." Journal of Neurophysiology, vol. 100, no. 4, 2008, pp. 2300-11.
Hamamoto DT, Khasabov SG, Cain DM, et al. Tumor-evoked sensitization of C nociceptors: a role for endothelin. J Neurophysiol. 2008;100(4):2300-11.
Hamamoto, D. T., Khasabov, S. G., Cain, D. M., & Simone, D. A. (2008). Tumor-evoked sensitization of C nociceptors: a role for endothelin. Journal of Neurophysiology, 100(4), 2300-11. https://doi.org/10.1152/jn.01337.2007
Hamamoto DT, et al. Tumor-evoked Sensitization of C Nociceptors: a Role for Endothelin. J Neurophysiol. 2008;100(4):2300-11. PubMed PMID: 18684911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-evoked sensitization of C nociceptors: a role for endothelin. AU - Hamamoto,Darryl T, AU - Khasabov,Sergey G, AU - Cain,David M, AU - Simone,Donald A, Y1 - 2008/08/06/ PY - 2008/8/8/pubmed PY - 2008/12/17/medline PY - 2008/8/8/entrez SP - 2300 EP - 11 JF - Journal of neurophysiology JO - J Neurophysiol VL - 100 IS - 4 N2 - 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. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/18684911/Tumor_evoked_sensitization_of_C_nociceptors:_a_role_for_endothelin_ L2 - https://journals.physiology.org/doi/10.1152/jn.01337.2007?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -