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Review

The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents

1
Department of Anesthesiology, Advocate Illinois Masonic Medical Center, 836 W. Wellington Ave. Suite 4815, Chicago, IL 60657, USA
2
Department of Anesthesiology, University of Illinois, Chicago, IL 60612, USA
3
Department of Surgery, University of Illinois, Chicago, IL 60612, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6045; https://doi.org/10.3390/ijms21176045
Received: 22 July 2020 / Revised: 11 August 2020 / Accepted: 19 August 2020 / Published: 22 August 2020
(This article belongs to the Special Issue Decoding the Complex Crossroad of Tryptophan Metabolic Pathways)
Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life. View Full-Text
Keywords: tryptophan; kynurenine; IDO-1; IDO-2; KMO; chronic pain; depression; metabolic pathway tryptophan; kynurenine; IDO-1; IDO-2; KMO; chronic pain; depression; metabolic pathway
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MDPI and ACS Style

Jovanovic, F.; Candido, K.D.; Knezevic, N.N. The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents. Int. J. Mol. Sci. 2020, 21, 6045. https://doi.org/10.3390/ijms21176045

AMA Style

Jovanovic F, Candido KD, Knezevic NN. The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents. International Journal of Molecular Sciences. 2020; 21(17):6045. https://doi.org/10.3390/ijms21176045

Chicago/Turabian Style

Jovanovic, Filip, Kenneth D. Candido, and Nebojsa N. Knezevic. 2020. "The Role of the Kynurenine Signaling Pathway in Different Chronic Pain Conditions and Potential Use of Therapeutic Agents" International Journal of Molecular Sciences 21, no. 17: 6045. https://doi.org/10.3390/ijms21176045

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