The Role of Kynurenine and Its Metabolites in Comorbid Chronic Pain and Depression

Athnaiel, Onella; Ong, Charmaine; Knežević, Nebojša Nick

doi:10.3390/metabo12100950

Cited by 9 publications

(11 citation statements)

References 47 publications

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“…There are several factors that could be further researched in relation to this, such as depression, mood, and anxiety levels in cancer patients with chronic pain. Depression and anxiety have been found to affect quinolinic acid levels, as shown in studies by Steiner et al (2011) and Athnaiel et al (2022), which found an association between depression and quinolinic acid levels in the brain.…”

Section: Relationship Between Quinolinic Acid Level and Pain Intensitymentioning

confidence: 85%

Quinolinic Acid and Chronic Cancer Pain

2023

JPTCP

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Pain is a complex phenomenon that is influenced by both objective and subjective factors. In patients with cancer undergoing active therapy, the prevalence of chronic pain is estimated to range from 30% to 50%. Given the complex nature of cancer patients' conditions, including impaired physical function, psychological distress, and various other problems, a comprehensive pain assessment is necessary to ensure effective pain management, reduce morbidity, and prevent opioid dependence. Objective measurement of pain is essential to improve the quality of chronic pain services for malignancy, and several biomarkers have been identified as potentially useful tools for measuring chronic pain more objectively. Quinolinic acid is one of these significant biomarkers that have been found to be useful for assessing pain. This study represents the first investigation in Indonesia of the relationship between quinolinic acid and chronic cancer pain. A cross-sectional study was conducted with 85 participants, including 29 male and 56 female patients. The pain scale was measured using the Numerating Rating Scale (NRS) with a range of 0-10, and serum quinolinic acid levels were measured using ELISA. Of the 85 study participants, 29 patients (34.12%) had pelvic organ cancer, 21 patients (24.71%) had head and neck cancer, 12 patients (14.12%) had abdominal organ cancer, 7 patients (8.24%) had breast cancer, 5 patients (5.88%) had pulmonary cancer, 4 patients (4.71%) had skin cancer, and 7 patients (8.24%) had other types of cancer. The study found that the effect of quinolinic acid on the degree of pain was significant (p = 0.024), with a correlation coefficient (r) of 0.244. However, the effect of kynurenic acid on the duration of pain was not significant (p = 0.135). In conclusion, quinolinic acid was found to be correlated with the degree of pain in chronic cancer patients, but it had no correlation with the duration of pain. Further research is needed to explore the potential of quinolinic acid as a biomarker for chronic pain assessment and management in cancer patients.

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Section: Relationship Between Quinolinic Acid Level and Pain Intensitymentioning

confidence: 85%

Quinolinic Acid and Chronic Cancer Pain

2023

JPTCP

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“…QA, which could be a major contributor to depression, is associated with neuroinflammation, depression, and neurodegeneration. Raised values have been observed together with inflammatory markers in several neurodegenerative diseases [ 10 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Proinflammatory cytokines upregulate IDO expression and shunt the tryptophan metabolism toward the inflammatory markers Kyn and QA [ 1 , 3 ]. Kyn is also metabolised to KA, which has been ascribed neuroprotective, anti-inflammatory and diabetogenic effects [ 10 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…Deviating tryptophan metabolism is observed in various disorders with common pathophysiological characteristics, such as immune system activation [ 1 , 2 , 3 ]. Obesity, depression, and chronic obstructive pulmonary disease (COPD) are disorders with changes in the KP [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. These diseases were chosen because they have shown changes in the KP indicating inflammation, and we had data from ongoing studies that allowed comparisons of the KP.…”

Section: Introductionmentioning

confidence: 99%

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The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease

et al. 2023

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Background: Changes in tryptophan metabolism through the kynurenine pathway (KP) canis observed in several disorders and coupled with pathophysiological deviations. Methods: This study retrospectively compared the KP in serum in healthy subjects (108) with subjects with obesity (141), depression (49), and chronic obstructive pulmonary disease (COPD) (22) participating in four clinical studies and explored predictors of the changes in the KP metabolites. Results: Compared with the healthy group, the KP was upregulated in the disease groups with high kynurenine, quinolinic acid (QA), kynurenine/tryptophan-ratio and QA/xanthurenic acid-ratio and low kynurenic acid/QA-ratio. Tryptophan and xanthurenic acid were upregulated in the depressed group compared with the groups with obesity and COPD. The covariates BMI, smoking, diabetes, and C-reactive protein explained the significant differences between the healthy group and the group with obesity but not between the healthy group and the groups with depression and COPD, indicating that different pathophysiological conditions result in the same changes in the KP. Conclusions: The KP was significantly upregulated in the disease groups compared with the healthy group, and there were significant differences between the disease groups. Different pathophysiological abnormalities seemed to result in the same deviations in the KP.

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“…The levels and ratios between different metabolites of the KP have been implicated in comorbid chronic pain and depression [ 39 ]. A large meta-analysis of 101 studies elaborated on the shift of TRP metabolism from serotonin to the KP and demonstrated decreased TRP and KYN across major depressive disorder (MDD), bipolar disorder, and schizophrenia [ 40 ].…”

Section: The Metabolic Pathways Of Trp: Kp and Serotonin Pathwaymentioning

confidence: 99%

Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions

Jovanovic¹,

Jovanovic

Knezevic

2023

Cells

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The pathogenesis of chronic pain entails a series of complex interactions among the nervous, immune, and endocrine systems. Defined as pain lasting or recurring for more than 3 months, chronic pain is becoming increasingly more prevalent among the US adult population. Pro-inflammatory cytokines from persistent low-grade inflammation not only contribute to the development of chronic pain conditions, but also regulate various aspects of the tryptophan metabolism, especially that of the kynurenine pathway (KP). An elevated level of pro-inflammatory cytokines exerts similar regulatory effects on the hypothalamic–pituitary–adrenal (HPA) axis, an intricate system of neuro–endocrine–immune pathways and a major mechanism of the stress response. As the HPA axis counters inflammation through the secretion of endogenous cortisol, we review the role of cortisol along with that of exogenous glucocorticoids in patients with chronic pain conditions. Considering that different metabolites produced along the KP exhibit neuroprotective, neurotoxic, and pronociceptive properties, we also summarize evidence rendering them as reliable biomarkers in this patient population. While more in vivo studies are needed, we conclude that the interaction between glucocorticoid hormones and the KP poses an attractive venue of diagnostic and therapeutic potential in patients with chronic pain.

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The Role of Kynurenine and Its Metabolites in Comorbid Chronic Pain and Depression

Cited by 9 publications

References 47 publications

Quinolinic Acid and Chronic Cancer Pain

Quinolinic Acid and Chronic Cancer Pain

The Kynurenine Pathway in Healthy Subjects and Subjects with Obesity, Depression and Chronic Obstructive Pulmonary Disease

Glucocorticoid Hormones as Modulators of the Kynurenine Pathway in Chronic Pain Conditions

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