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Evidence for the endothelin system as an emerging therapeutic target for the treatment of chronic pain

Authors Smith T, Haymond T, Smith S, Sweitzer S

Received 10 April 2014

Accepted for publication 5 May 2014

Published 30 August 2014 Volume 2014:7 Pages 531—545

DOI https://doi.org/10.2147/JPR.S65923

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3


Terika P Smith,1 Tami Haymond,1 Sherika N Smith,1 Sarah M Sweitzer1,2

1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, USA; 2Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA

Abstract: Many people worldwide suffer from pain and a portion of these sufferers are diagnosed with a chronic pain condition. The management of chronic pain continues to be a challenge, and despite taking prescribed medication for pain, patients continue to have pain of moderate severity. Current pain therapies are often inadequate, with side effects that limit medication adherence. There is a need to identify novel therapeutic targets for the management of chronic pain. One potential candidate for the treatment of chronic pain is therapies aimed at modulating the vasoactive peptide endothelin-1. In addition to vasoactive properties, endothelin-1 has been implicated in pain transmission in both humans and animal models of nociception. Endothelin-1 directly activates nociceptors and potentiates the effect of other algogens, including capsaicin, formalin, and arachidonic acid. In addition, endothelin-1 has been shown to be involved in inflammatory pain, cancer pain, neuropathic pain, diabetic neuropathy, and pain associated with sickle cell disease. Therefore, endothelin-1 may prove a novel therapeutic target for the relief of many types of chronic pain.

Keywords: endothelin-1, acute pain, chronic pain, endothelin receptor antagonists

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