Table 1.

Summary of kynurenine pathway metabolites and metabolite ratios as potential biomarkers in chronic pain.

Metabolite	Clinical Significance	Chronic Pain Implications	Mechanism
Quinolinic acid (QA)		Hyperalgesia development Comorbid chronic pain with neurodegenerative and psychiatric disorders	Excitotoxin via NMDA receptor agonism [39]
	Cytokine-mediated chronic inflammation		Self-potentiation of neurotoxicity via interference of glutamate–glutamine cycle [46]
			Elevated levels involved in neuronal cytoskeleton destabilization and apoptosis [40]
Kynurenic acid (KA)	Cytokine-mediated chronic inflammation	Neuroprotective properties Diminished levels possibly indicate poor inflammatory regulation with subsequent pain exacerbation Elevated levels possibly indicate upregulation for initial response to pain	Anti-excitotoxin via noncompetitive NMDA receptor antagonism [51]
			Anti-inflammatory via GPR35-mediated agonism [58] Downregulation of PI3K/Akt and MAPK pathways (inflammatory) [59] Upregulation of β-catenin accumulation (anti-inflammatory) [66]
Kynurenic acid/Quinolinic acid ratio (KA/QA)	Cytokine-mediated chronic inflammation Neurotoxicity	Lower KA/QA ratios indicate a lack of neuroprotection with subsequent pain exacerbation	Inadequate neuroprotective response via overactivity of QA production relative to KA production [68]
Kynurenine/Tryptophan ratio (KYN/Trp)	Cytokine-mediated chronic inflammation	Higher KYN/Trp ratios indicate elevated pain intensity	Upregulated IDO levels shunt available Trp away from serotonin production and towards the KP [70]