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Review

The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives

Department of Pain Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland
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Authors to whom correspondence should be addressed.
Academic Editor: István Szatmári
Int. J. Mol. Sci. 2021, 22(20), 11055; https://doi.org/10.3390/ijms222011055
Received: 15 September 2021 / Revised: 8 October 2021 / Accepted: 9 October 2021 / Published: 13 October 2021
(This article belongs to the Special Issue Synthesis and Transformations of Bioactive Hydroxyquinolines)
Accumulating evidence suggests the key role of the kynurenine pathway (KP) of the tryptophan metabolism in the pathogenesis of several diseases. Despite extensive research aimed at clarifying the mechanisms underlying the development and maintenance of neuropathic pain, the roles of KP metabolites in this process are still not fully known. Although the function of the peripheral KP has been known for several years, it has only recently been acknowledged that its metabolites within the central nervous system have remarkable consequences related to physiology and behavior. Both the products and metabolites of the KP are involved in the pathogenesis of pain conditions. Apart from the neuroactive properties of kynurenines, the KP regulates several neurotransmitter systems in direct or indirect ways. Some neuroactive metabolites are known to have neuroprotective properties (kynurenic acid, nicotinamide adenine dinucleotide cofactor), while others are toxic (3-hydroxykynurenine, quinolinic acid). Numerous animal models show that modulation of the KP may turn out to be a viable target for the treatment of diseases. Importantly, some compounds that affect KP enzymes are currently described to possess analgesic properties. Additionally, kynurenine metabolites may be useful for assessing response to therapy or as biomarkers in therapeutic monitoring. The following review describes the molecular site of action and changes in the levels of metabolites of the kynurenine pathway in the pathogenesis of various conditions, with a particular emphasis on their involvement in neuropathy. Moreover, the potential clinical implications of KP modulation in chronic pain therapy as well as the directions of new research initiatives are discussed. View Full-Text
Keywords: tryptophan; kynurenines; neuropathy; metabolic pathway; analgesia; kynurenic acid; 3-hydroxykynurenine; quinolinic acid; neuropathy tryptophan; kynurenines; neuropathy; metabolic pathway; analgesia; kynurenic acid; 3-hydroxykynurenine; quinolinic acid; neuropathy
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MDPI and ACS Style

Ciapała, K.; Mika, J.; Rojewska, E. The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives. Int. J. Mol. Sci. 2021, 22, 11055. https://doi.org/10.3390/ijms222011055

AMA Style

Ciapała K, Mika J, Rojewska E. The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives. International Journal of Molecular Sciences. 2021; 22(20):11055. https://doi.org/10.3390/ijms222011055

Chicago/Turabian Style

Ciapała, Katarzyna, Joanna Mika, and Ewelina Rojewska. 2021. "The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives" International Journal of Molecular Sciences 22, no. 20: 11055. https://doi.org/10.3390/ijms222011055

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