Kynurenic acid as chronic pain biomarker for future cancer pain management

Christrijogo Soemartono Waloejo; Nancy Margarita Rehatta; Lucky Andriyanto; Soni Sunarso Sulistiawan; Widodo J. Pudjirahardjo; Aditya B. Farhan; Hamidah Kurniasari; Yi-Hung Chen

doi:10.53730/ijhs.v6nS5.11277

Authors

Christrijogo Soemartono Waloejo Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya 60132, Indonesia
Nancy Margarita Rehatta Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya 60132, Indonesia.
Lucky Andriyanto
lucky-andriyanto@fk.unair.ac.id
Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya 60132, Indonesia.
Soni Sunarso Sulistiawan Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya 60132, Indonesia, Graduate Institute of Biomedical Sciences-China Medical University, Taiwan 40402, R.O.C.
Widodo J. Pudjirahardjo Public Health Faculty, Universitas Airlangga, Indonesia.
Aditya B. Farhan Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya 60132, Indonesia.
Hamidah Kurniasari Department of Anesthesiology and Reanimation, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Hospital, Surabaya 60132, Indonesia.
Yi-Hung Chen Graduate Institute of Acupuncture Science-China Medical University, Taiwan 40402, R.O.C.

Abstract

The prevalence of chronic pain ranges from 30-50% in patients with cancer undergoing active therapy. Kynurenic acid, xanthurenic acid, and quinolinic acid are significant biomarkers for assessing pain objectively. This study aims to investigate the scientific evidence of the effect of serum kynurenic acid levels on the severity and duration of chronic cancer pain. It is a cross-sectional study with 80 subjects consisting of 19 male and 61 female patients in the palliative outpatient clinic of Dr Soetomo Hospital. The pain assessment was performed using the NRS, and the biochemical analysis of serum kynurenic acid was assessed using the ELISA method. Of the total of 80 subjects, 26 patients had pelvic organ cancer (33.7%), 24 patients had respiratory organ cancer (30.1%), 17 patients had breast cancer (21.7%), 9 patients had abdominal organ cancer (9.6%), 3 patients had malignant melanoma (3.6%), and 1 patient had sternal bone cancer (1.2%). Kynurenic acid significantly correlated with the severity of pain (p = 0.043), with (r) of -0.218. However, kynurenic acid showed no significant correlation with the duration of pain (p = 0.052). Kynurenic acid affected the severity of pain but did not affect the duration of pain in chronic cancer pain patients.

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References

Amirdelfan, K., Pope, J. E., Gunn, J., Hill, M. M., Cotton, B. M., Beresh, J. E. (2020). Clinical validation of multi-biomarker assay for the evaluation of chronic pain patients in a cross-sectional observational study. Pain Ther, 9(2), 511-29. doi: 10.1007/s40122-020-00175-3.

Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. (2020). Acute Pain Management: Scientific Evidence. 5th ed. Melbourne: ANZCA & FPM.

Badawy, A. A., Dougherty, D. M. (2016). Assessment of the Human Kynurenine Pathway: Comparisons and Clinical Implications of Ethnic and Gender Differences in Plasma Tryptophan, Kynurenine Metabolites, and Enzyme Expressions at Baseline and After Acute Tryptophan Loading and Depletion. Int J Tryptophan Res,10(9), 31-49. doi: 10.4137/IJTR.S38189.

Bostian, A. and Eoff, R. (2016). Aberrant kynurenine signaling modulates DNA replication stress factors and promotes genomic instability in gliomas. Chem Res Toxicol, 29(9), 1369–80. doi: 10.1021/acs.chemrestox.6b00255.

Dahlhamer, J., Lucas, J., Zelaya, C., Nahin, R., Mackey, S., DeBar, L. (2018). Prevalence of chronic pain and high-impact chronic pain among adults-United States. MMWR Morb Mortal Wkly Rep, 67(36), 1001-6. doi: 10.15585/mmwr.mm6736a2.

Davis, I. and Liu, A. (2015). What is the tryptophan kynurenine pathway and why is it important to neurotherapy? Expert Rev Neurother, 5(7), 719–21. doi: 10.1586/14737175.2015.1049999.

Deac, O., James, L., Barry, S., Øivind, M., Per, M., John, T., Margaret, E., Eamon, L., Eileen, R., Ruzong, F., Yifan, W., Lawrence, C., Anne, M. (2015). Tryptophan Catabolism and Vitamin B-6 Status Are Affected by Gender and Lifestyle Factors in Healthy Young Adults. J Nutr, 145(4), 701-7. doi: 10.3945/jn.114.203091.

Evrensel, A., Önen, Ü., Emin, C. (2020). Anxiety Disorders Immune Kynurenine Pathways and the Gut Microbiota-Brainn Axis Chapter in Advances in Experimental Medicine and Biology in Anxiety Disorders. Singapore: Springer.

Favennec, M., Benjamin, H., Robert, C., Audrey, L., Loic, Y., Marie, V., Abdelilah, A., Michel, M., Marie, P., Alban, B., Gilles, J., Giulia, C., Bart, S., Franc¸ ois, P., Beverley, B. (2015). The Kynurenine Pathway is Activated in Human Obesity and Shifted Toward Kynurenine Monooxygenase Activation. Original Article: Obesity Biology and Integrated Physiology, 23(10). 2066-74. doi: 10.1002/oby.21199.

Gelman, D., Gelmanas, A., Urbanaitė, D., Tamošiūnas, R., Sadauskas, S., Bilskienė, D., Naudžiūnas, A., Širvinskas, E., Benetis, R., Macas, A. (2018). Role of Multimodal Analgesia in the Evolving Enhanced Recovery Chronic Pain Pathways. Medicina, 54(2), 20. doi: 10.3390/medicina54020020.

Gostner, J. M., Becker, K., Überall, F., Fuchs, D. (2015). The potential of targeting indoleamine 2,3-dioxygenase for cancer treatment. Expert Opin Ther Targets, 19(5), 605–15. doi: 10.1517/14728222.2014.995092.

Greco, Maria, T., Anna, R., Oscar, C. (2014). Quality of Cancer Pain Management: An Update of a Systematic Review of Undertreatment of Patients with Cancer. J Clin Oncol, 32(36), 4149-54. doi: 10.1200/JCO.2014.56.0383.

Gunn, J., Hill, M. M., Cotton, B. M., Deer, T. R. (2020). An Analysis of Biomarkers in Patients with Chronic Pain. Pain Physician, 23(1), E41-E49.

Haefeli, M., Elfering, A. (2018). Pain Assesment. International Association for the Study of Pain, 15(1), 17-24.

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

Kim, S., Miller, B. J., Stefanek, M. E., Miller, A. H. (2015). Inflammation-induced activation of the indoleamine 2,3-dioxygenase pathway: relevance to cancer-related fatigue. Cancer, 121: 2129–36. doi: 10.1002/cncr.29302

Meissner, W., Huygen, F., Neugebauer, E., Osterbrink, J., Benhamou, D., Betteridge, N. (2018). Management of acute pain in the postoperative setting: the importance of quality indicators. Current Medical Research and Opinion, 34 (1), 187-96. doi: 10.1080/03007995.2017.1391081.

Miller, A. H., Ancoli-Israel, S., Bower, J. E., Capuron, L., Irwin, M. R. (2008). Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol, 26, 971–82. doi: 10.1200/JCO.2007.10.7805.

Peter, G., Niamh, A., Paulo, R. (2018). The Edmonton Classification System for Cancer Pain: a tool with potential for an evolving role in cancer pain assessment and management. Expert review of quality of life in cancer care, 3:2-3, 47-64. doi: 10.1080/23809000.2018.1467211.

Phillips, C., J. (2019). The cost and burden of chronic pain. Reviews in Pain, 3(1), 2-5. doi: 10.1177/204946370900300102.

Prendergast, G. C., Malachowski, W. P., DuHadaway, J. B., Muller, A. J. (2017). Discovery of IDO1 inhibitors: from bench to bedside. Cancer Res, 77(24), 6795–811. doi: 10.1158/0008-5472.CAN-17-2285.

Rodriguez, C., Ming, J., Hsiao-Lan, W., Tapan, P., Susan, C., McMillan. (2019). Cancer Pain and Quality of Life. Symptom Management Series, 21, 1-8.

Savitz, J. (2020). The kynurenine pathway: A finger in every pie. Mol Psychiatry, 25(1), 131-47. doi: 10.1038/s41380-019-0414-4.

Suryasa, I. W., Rodríguez-Gámez, M., & Koldoris, T. (2021). Get vaccinated when it is your turn and follow the local guidelines. International Journal of Health Sciences, 5(3), x-xv. https://doi.org/10.53730/ijhs.v5n3.2938

Thaib, P. K. P., & Rahaju, A. S. (2022). Clinicopathological profile of clear cell renal cell carcinoma. International Journal of Health & Medical Sciences, 5(1), 91-100. https://doi.org/10.21744/ijhms.v5n1.1846

Sforzini, L., Nettis, M. A., Mondelli, V., Pariante, C. M. (2019). Inflammation in cancer and depression: a starring role for the kynurenine pathway. Psychopharmacology, 236(10), 2997-3011. doi: 10.1007/s00213-019-05200-8.

Sofia, C., Inês, D., Andrea, A., Sandra, D., Agnès, A., Cédric, B., Damien, F., Patrick, L., Eric, M., Fulvio, M., Lucile, C.. (2020). Tryptophan Metabolic Pathways Are Altered in Obesity and Are Associated with Systemic Inflammation. Front Immunol, 11, 557. doi: 10.3389/fimmu.2020.00557.

Szucs, E., Azzurra, S., Marilisa, P., Ferenc, Z., Stefano, P., Gokhan, Z., László, V., Sándor, B., Marianna, N., Adriano, M. (2020). Discovery of Kynurenines Containing Oligopeptides as Potent Opioid Receptor Agonists. Biomolecules, 10(2), 284. doi: 10.3390/biom10020284.

Triplett, T. A., Garrison, K. C., Marshall, N., Donkor, M., Blazeck, J., Lamb, C. (2018). Reversal of indoleamine 2,3-dioxygenase–mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme. Nat Biotechnol, 36(8), 758-64. doi: 10.1038/nbt.4180.

Vadivelu, N., Alice, M., Gopal, K., Karine, B., Manuel, F., Matthew, M. (2017). Pain and Psychology—A Reciprocal Relationship. Ochsner Journal, 17(2), 173–80.

Vescei, L., Szalardy, L., Fulop, F., Toldi, J. (2013). Kynurenines in the CNS: recent advances and new questions. Nature Reviews Drug Discovery, 12 (1), 64-82. doi: 10.1038/nrd3793.