111: Exploring serotonin, melatonin and cortisol as biomarkers for chronic musculoskeletal pain

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, , , , , , Assessment and Measurement of Pain/Nociception, , ,

Background and Aims: Chronic musculoskeletal pain (CMP) is a complex condition, generally measured by subjective measures. Recent advances have been made in understanding CMP on a biophysiological level. It is becoming evident that understanding biomarkers i.e. serotonin, melatonin, and cortisol in CMP can provide an objective way in which to better understand the biological factors which affect CMP. However little remains known about this topic. The aim of the study was preliminarily explore the relationship between the biomarker concentration levels (i.e., serotonin, melatonin, and cortisol), and self-reported musculoskeletal pain, sleep quality and mood in a population of undergraduate students with/without pain in Qatar.

Methods: A cross-sectional observational laboratory-based study was conducted at Qatar University, Qatar. Recruitment of participants took place through official university email, and direct recruitment campaigns. Undergraduate students (18–25 years) with/without CMP were invited to participate. Blood samples were collected and analyzed in the university's clinical laboratory. Levels of cortisol, melatonin and serotonin were measured. Participants completed a questionnaire which included information about sociodemographic data, lifestyle behaviors, pain characteristics, etc. Information about the interference of pain on mood, sleep, etc. was also collected. Participants were categorized into three groups - No Pain (NP), Acute Pain (AP) and Chronic Pain (CP) groups.

Results: Mean (SD) cortisol levels were 10.84 μg/dL (±4.50) in the NP group, 11.62 μg/dL (±5.65) in AP group, and 9.85 μg/dL (±2.72) in the CP group. Cortisol was slightly higher in NP than CP (MD 0.99 μg/dL) and slightly lower than AP (MD −0.78 μg/dL), with all values within normative ranges (6.41–22.83 μg/dL) and no significant differences (p<0.05). Differences in serotonin and melatonin levels between groups were also non-significant, with small mean differences and wide confidence intervals, indicating comparable biomarker profiles across groups.

Conclusions: This study underscores the critical need for more comprehensive and methodologically robust investigations into the complex interplay between physiological biomarkers, subjective pain experiences, and psychological factors in individuals with chronic musculoskeletal pain (CMP). Chronic pain is increasingly understood as a multidimensional condition, shaped not only by peripheral tissue pathology but also by neurobiological processes, affective states, cognitive appraisals, and sociocultural influences. However, the precise nature of the relationships among biological markers (e.g., inflammatory cytokines, cortisol levels, autonomic indicators), self-reported pain intensity and disability, and psychological constructs such as pain catastrophizing, fear-avoidance, anxiety, and depression remains insufficiently elucidated.

References: Abboud, M. (2022). Vitamin D Supplementation and Sleep: A Systematic Review and Meta-Analysis of Intervention Studies. Nutrients, 14(5), 1076. https://doi.org/10.3390/nu14051076
Al’Absi, M. (2006). Hypothalamic–pituitary–adrenocortical responses to psychological stress and risk for smoking relapse. International Journal of Psychophysiology, 59(3), 218–227. https://doi.org/10.1016/j.ijpsycho.2005.10.010
Alhalal, E. A., Alhalal, I. A., Alaida, A. M., Alhweity, S. M., Alshojaa, A. Y., & Alfaori, A. T. (2021). Effects of chronic pain on sleep quality and depression. Saudi Medical Journal, 42(3), 315–323. https://doi.org/10.15537/smj.42.3.20200768
Al-Yatama, F. I., AlOtaibi, F., Al-Bader, M. D., & Al-Shoumer, K. A. (2019). The effect of clothing on vitamin D status, bone turnover markers, and bone mineral density in young Kuwaiti females. International Journal of Endocrinology, 2019, 1–10. https://doi.org/10.1155/2019/6794837
Arendt, J., & Aulinas, A. (2022). Physiology of the pineal gland and melatonin. Endotext - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK550972/
Ashaye, T., Hounsome, N., Carnes, D., Taylor, S. J. C., Homer, K., Eldridge, S., Spencer, A., Rahman, A., Foell, J., & Underwood, M. R. (2018). Opioid prescribing for chronic musculoskeletal pain in UK primary care: results from a cohort analysis of the COPERS trial. BMJ Open, 8(6), e019491. https://doi.org/10.1136/bmjopen-2017-019491
Auyeung, A., Wang, H. C., Aravagiri, K., & Knezevic, N. N. (2023). Kynurenine pathway metabolites as potential biomarkers in chronic pain. Pharmaceuticals, 16(5), 681. https://doi.org/10.3390/ph16050681
Azmi, N. a. S. M., Juliana, N., Azmani, S., Effendy, N. M., Abu, I. F., Teng, N. I. M. F., & Das, S. (2021). Cortisol on circadian rhythm and its effect on cardiovascular system. International Journal of Environmental Research and Public Health, 18(2), 676. https://doi.org/10.3390/ijerph18020676
Baklola, M., Terra, M., Al-Barqi, M., AbdulHusain, Y. H., Asiri, S. A., Jadaan, N. S., Haroona, A., Almosawi, S., & Ahmari, S. S. A. (2024). Prevalence of insomnia among university students in Saudi Arabia: a systematic review and meta‑analysis. The Egyptian Journal of Neurology Psychiatry and Neurosurgery, 60(1). https://doi.org/10.1186/s41983-024-00914-9
Bamalan, O. A., Moore, M. J., & Khalili, Y. A. (2023). Physiology, serotonin. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK545168/
Benloucif, S., Burgess, H. J., Klerman, E. B., Lewy, A. J., Middleton, B., Murphy, P. J., Parry, B. L., & Revell, V. L. (2008). Measuring melatonin in humans. https://pmc.ncbi.nlm.nih.gov/articles/PMC2276833/
Benowitz, N. L. (2010). Nicotine addiction. The New England Journal of Medicine, 362(24), 2295–2303. https://doi.org/10.1056/NEJMra0809890
Bodaghi, A., Fattahi, N., & Ramazani, A. (2023). Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon, 9(2), e13323. https://doi.org/10.1016/j.heliyon.2023.e13323
Chaudhry, S. R., Stadlbauer, A., Buchfelder, M., & Kinfe, T. M. (2021). Melatonin moderates the triangle of chronic pain, sleep architecture and immunometabolic traffic. Biomedicines, 9(8), 984. https://doi.org/10.3390/biomedicines9080984
Chen, Q., Zhang, W., Sadana, N., & Chen, X. (2021). Estrogen receptors in pain modulation: Cellular signaling. Biology of Sex Differences, 12, 22. https://doi.org/10.1186/s13293-021-00364-5
Choi, J., Park, Y., Park, S. K., Lee, J.-S., Kim, J., Choi, J. I., Yoon, K. B., Lee, S.-S., Lim, D. E., Choi, J. Y., Kim, M., Park, G. H., Choi, S.-C., & Lee, J. (2017). Testosterone effects on pain and brain activation patterns. Acta Anaesthesiologica Scandinavica, 61(6), 668–675. https://doi.org/10.1111/AAS.12908
Cohen, S. P., Vase, L., & Hooten, W. M. (2021). Chronic pain: an update on burden, best practices, and new advances. The Lancet, 397(10289), 2082–2097. https://doi.org/10.1016/s0140-6736(21)00393-7
Cleeland, C. S., & Ryan, K. M. (1994). Pain assessment: global use of the Brief Pain Inventory. PubMed, 23(2), 129–138. https://pubmed.ncbi.nlm.nih.gov/8080219
Danilov, A., & Kurganova, J. (2016). Melatonin in chronic pain syndromes. Pain and Therapy, 5(1), 1–17. https://doi.org/10.1007/s40122-016-0049-y
De La Corte-Rodriguez, H., Roman-Belmonte, J. M., Resino-Luis, C., Madrid-Gonzalez, J., & Rodriguez-Merchan, E. C. (2024). The Role of Physical Exercise in Chronic Musculoskeletal Pain: Best Medicine—A Narrative Review. Healthcare, 12(2), 242. https://doi.org/10.3390/healthcare12020242
De La Rosa, J. S., Brady, B. R., Ibrahim, M. M., Herder, K. E., Wallace, J. S., Padilla, A. R., & Vanderah, T. W. (2023). Co-occurrence of chronic pain and anxiety/depression symptoms in U.S. adults: prevalence, functional impacts, and opportunities. Pain. https://doi.org/10.1097/j.pain.0000000000003056
De Lucena, J. M. S., Cheng, L. A., Cavalcante, T. L. M., Da Silva, V. A., & De Farias Júnior, J. C. (2015). Prevalência de tempo excessivo de tela e fatores associados em adolescentes. Revista Paulista De Pediatria, 33(4), 407–414. https://doi.org/10.1016/j.rpped.2015.04.001
Dewhurst, S. A., Anderson, R. J., & Knott, L. M. (2012). A gender difference in false recall of negative words: Women DRM more than men. Cognition and Emotion, 26(1), 65–74. https://doi.org/10.1080/02699931.2011.553037
Dunn, M., Rushton, A. B., Mistry, J., Soundy, A., & Heneghan, N. R. (2024). The biopsychosocial factors associated with development of chronic musculoskeletal pain. An umbrella review and meta-analysis of observational systematic reviews. PLoS ONE, 19(4), e0294830. https://doi.org/10.1371/journal.pone.0294830
Dzakpasu, F. Q. S., Carver, A., Brakenridge, C. J., Cicuttini, F., Urquhart, D. M., Owen, N., & Dunstan, D. W. (2021). Musculoskeletal pain and sedentary behaviour in occupational and non-occupational settings: a systematic review with meta-analysis. International Journal of Behavioral Nutrition and Physical Activity, 18(1). https://doi.org/10.1186/s12966-021-01191-y
Dziurkowska, E., & Wesolowski, M. (2021). Cortisol as a biomarker of mental disorder severity. Journal of Clinical Medicine, 10(21), 5204. https://doi.org/10.3390/jcm10215204
Edwards, R. R., Schreiber, K. L., Dworkin, R. H., Turk, D. C., Baron, R., Freeman, R., Jensen, T. S., Latremoliere, A., Markman, J. D., Rice, A. S. C., Rowbotham, M., Staud, R., Tate, S., Woolf, C. J., Andrews, N. A., Carr, D. B., Colloca, L., Cosma-Roman, D., Cowan, P., . . . Wesselmann, U. (2022). Optimizing and accelerating the development of precision pain treatments for chronic pain: IMMPACT review and recommendations. Journal of Pain, 24(2), 204–225. https://doi.org/10.1016/j.jpain.2022.08.010
El-Tallawy, S. N., Nalamasu, R., Salem, G. I., LeQuang, J. a. K., Pergolizzi, J. V., & Christo, P. J. (2021). Management of Musculoskeletal Pain: An Update with Emphasis on Chronic Musculoskeletal Pain. Pain and Therapy, 10(1), 181–209. https://doi.org/10.1007/s40122-021-00235-2
Fatoye, F., Gebrye, T., Ryan, C. G., Useh, U., & Mbada, C. (2023). Global and regional estimates of clinical and economic burden of low back pain in high-income countries: a systematic review and meta-analysis. Frontiers in Public Health, 11. https://doi.org/10.3389/fpubh.2023.1098100
Ferwati, S., Skelhorn, C., Shandas, V., Voelkel, J., Shawish, A., & Ghanim, M. (2017). Analysis of urban heat in a corridor environment – The case of Doha, Qatar. Urban Climate, 24, 692–702. https://doi.org/10.1016/j.uclim.2017.08.008
Finan, P. H., Goodin, B. R., & Smith, M. T. (2013). The Association of Sleep and Pain: An Update and a Path Forward. Journal of Pain, 14(12), 1539–1552. https://doi.org/10.1016/j.jpain.2013.08.007
Fischer, M. A., & Jan, A. (2023). Medication-Overuse headache. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK538150/
Gaskin, D. J., & Richard, P. (2011). The economic costs of pain in the United States. Relieving Pain in America - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK92521/#:~:text=We%20found%20that%20the%20total,from%20%24190.6%20to%20%24226.3%20billion).
Gavan, S. P., Thompson, A. J., & Payne, K. (2018). The economic case for precision medicine. Expert Review of Precision Medicine and Drug Development, 3(1), 1–9. https://doi.org/10.1080/23808993.2018.1421858
Grunspan, D. Z., Eddy, S. L., Brownell, S. E., Wiggins, B. L., Crowe, A. J., & Goodreau, S. M. (2016). Males under-estimate academic performance of their female peers in undergraduate biology classrooms. PLOS ONE, 11(2), e0148405. https://doi.org/10.1371/journal.pone.0148405
Gunn, J., M Hill, M., M Cotten, B., & R Deer, T. (2020). An Analysis of Biomarkers in Patients with Chronic Pain. Pain Physician, 23(1), E41–E49. https://pubmed.ncbi.nlm.nih.gov/32013287/
Haack, M., Simpson, N., Sethna, N., Kaur, S., & Mullington, J. (2019). Sleep deficiency and chronic pain: potential underlying mechanisms and clinical implications. Neuropsychopharmacology, 45(1), 205–216. https://doi.org/10.1038/s41386-019-0439-z
Hannibal, K. E., & Bishop, M. D. (2014). Chronic Stress, cortisol dysfunction, and pain: A Psychoneuroendocrine Rationale for Stress management in Pain Rehabilitation. Physical Therapy, 94(12), 1816–1825. https://doi.org/10.2522/ptj.20130597
Hao, S., Shi, W., Liu, W., Chen, Q., & Zhuo, M. (2023). Multiple modulatory roles of serotonin in chronic pain and injury-related anxiety. Frontiers in Synaptic Neuroscience, 15. https://doi.org/10.3389/fnsyn.2023.1122381
Harfmann, B. D., Schroder, E. A., & Esser, K. A. (2014). Circadian rhythms, the molecular clock, and skeletal muscle. Journal of Biological Rhythms, 30(2), 84–94. https://doi.org/10.1177/0748730414561638
Hermesdorf, M., Berger, K., Baune, B. T., Wellmann, J., Ruscheweyh, R., & Wersching, H. (2016). Pain sensitivity in patients with major depression: differential effect of pain sensitivity measures, somatic cofactors, and disease characteristics. Journal of Pain, 17(5), 606–616. https://doi.org/10.1016/j.jpain.2016.01.474
Hester, J., & Tang, N. K. Y. (2008). Insomnia Co-Occurring with Chronic Pain: Clinical Features, Interaction, Assessments and Possible Interventions. Reviews in Pain, 2(1), 2–7. https://doi.org/10.1177/204946370800200102
Huiberts, L. M., & Smolders, K. C. (2020). Effects of vitamin D on mood and sleep in the healthy population: Interpretations from the serotonergic pathway. Sleep Medicine Reviews, 55, 101379. https://doi.org/10.1016/j.smrv.2020.101379
Hussein, D., Ahmed, G., Ahmed, S., Salih, R., Kakamad, F., Salih, A., Amin, B. H., Abdalla, B., Mohammed, S., Salim, R., Hamarahim, S., Hamid, S., Hamarashid, A., Rashid, C., Hamadameen, W., & Salih, K. (2022). Pattern of vitamin D deficiency in a Middle Eastern population: A crosssectional study. International Journal of Functional Nutrition, 3(5). https://doi.org/10.3892/ijfn.2022.30
Jauhar, S., Cowen, P. J., & Browning, M. (2023). Fifty years on: Serotonin and depression. Journal of Psychopharmacology, 37(3), 237–241. https://doi.org/10.1177/02698811231161813
Jenkins, T., Nguyen, J., Polglaze, K., & Bertrand, P. (2016). Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients, 8(1), 56. https://doi.org/10.3390/nu8010056
Jiang, X., Zheng, X., Yang, J., Ye, C., Chen, Y., Zhang, Z., & Xiao, Z. (2015). A systematic review of studies on the prevalence of Insomnia in university students. Public Health, 129(12), 1579–1584. https://doi.org/10.1016/j.puhe.2015.07.030
Johnson, K. B., Wei, W., Weeraratne, D., Frisse, M. E., Misulis, K., Rhee, K., Zhao, J., & Snowdon, J. L. (2020). Precision medicine, AI, and the future of personalized health care. Clinical and Translational Science, 14(1), 86–93. https://doi.org/10.1111/cts.12884
Malcheva, K., & Bocheva, L. (2023). Assessment of Contemporary Climate Change in Bulgaria Using the Köppen-Geiger Climate Classification. In Lecture notes in networks and systems (pp. 137–148). https://doi.org/10.1007/978-3-031-26754-3_12
Malebari, A. M., Alamoudi, S. O., Al-Alawi, T. I., Alkhateeb, A. A., Albuqayli, A. S., & Alothmany, H. N. (2024). Prevalence of depression and anxiety among university students in Jeddah, Saudi Arabia: exploring sociodemographic and associated factors. Frontiers in Public Health, 12. https://doi.org/10.3389/fpubh.2024.1441695
Marx, D. M., & Stapel, D. A. (2006). It depends on your perspective: The role of self-relevance in stereotype-based underperformance. Journal of Experimental Social Psychology, 42(6), 768–775. https://doi.org/10.1016/j.jesp.2005.08.005
Mills, S. E., Nicolson, K. P., & Smith, B. H. (2019). Chronic pain: a review of its epidemiology and associated factors in population-based studies. British Journal of Anaesthesia, 123(2), e273–e283. https://doi.org/10.1016/j.bja.2019.03.023
Minich, D. M., Henning, M., Darley, C., Fahoum, M., Schuler, C. B., & Frame, J. (2022). Is melatonin the “Next vitamin D”?: A review of emerging science, clinical uses, safety, and dietary supplements. Nutrients, 14(19), 3934. https://doi.org/10.3390/nu14193934
Muhtz, C., Rodriguez-Raecke, R., Hinkelmann, K., Moeller-Bertram, T., Kiefer, F., Wiedemann, K., May, A., & Otte, C. (2012). Cortisol Response to Experimental Pain in Patients with Chronic Low Back Pain and Patients with Major Depression. Pain Medicine, 14(4), 498–503. https://doi.org/10.1111/j.1526-4637.2012.01514.x
National Toxicology Program. (2021, April 1). Light at night and night shift work: Circadian Disruption studies. NTP Cancer Hazard Assessment Report on Night Shift Work and Light at Night - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK571600/
NCI Dictionary of Cancer Terms. (n.d.). Cancer.gov. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biomarker
O’Sullivan, P., Beales, D., Jensen, L., Murray, K., & Myers, T. (2011). Characteristics of chronic non-specific musculoskeletal pain in children and adolescents attending a rheumatology outpatients clinic: a cross-sectional study. Pediatric Rheumatology, 9(1). https://doi.org/10.1186/1546-0096-9-3
Paananen, M., O’Sullivan, P., Straker, L., Beales, D., Coenen, P., Karppinen, J., Pennell, C., & Smith, A. (2015). A low cortisol response to stress is associated with musculoskeletal pain combined with increased pain sensitivity in young adults: a longitudinal cohort study. Arthritis Research & Therapy, 17(1). https://doi.org/10.1186/s13075-015-0875-z
Permanent Committee for Islamic Research and Ifta. (2006). Fatwa No. 18142 [Smoking]. Retrieved from https://www.alifta.gov.sa/
Qaseem, A., Wilt, T. J., McLean, R. M., & Forciea, M. A. (2017). Noninvasive treatments for acute, subacute, and chronic low back pain: A clinical practice guideline from the American College of Physicians. Annals of Internal Medicine, 166(7), 514–530. https://doi.org/10.7326/M16-2367
Runge, N., Ahmed, I., Saueressig, T., Perea, J., Labie, C., Mairesse, O., Nijs, J., Malfliet, A., Verschueren, S., Van Assche, D., De Vlam, K., Van Waeyenberg, T., Van Haute, J., & De Baets, L. (2024). The bidirectional relationship between sleep problems and chronic musculoskeletal pain: a systematic review with meta-analysis. Pain, 165(11), 2455–2467. https://doi.org/10.1097/j.pain.0000000000003279
Sasaki, M., Kamiya, Y., Bamba, K., Onishi, T., Matsuda, K., Kohno, T., Kurabe, M., Furutani, K., & Yanagimura, H. (2021). Serotonin plays a key role in the development of Opioid-Induced hyperalgesia in mice. Journal of Pain, 22(6), 715–729. https://doi.org/10.1016/j.jpain.2020.12.008
Savage, R. A., Zafar, N., Yohannan, S., & Miller, J. M. (2024, February 9). Melatonin. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK534823/#:~:text=Melatonin%20regulates%20the%20body's%20sleep,its%20MT1%20and%20MT2%20receptors.
Seiger, A. N., Penzel, T., & Fietze, I. (2024). Chronic pain management and sleep disorders. Cell Reports Medicine, 5(10), 101761. https://doi.org/10.1016/j.xcrm.2024.101761
Serbic, D., Friedrich, C., & Murray, R. (2021). Psychological, social and academic functioning in university students with chronic pain: A systematic review. Journal of American College Health, 71(9), 2894–2908. https://doi.org/10.1080/07448481.2021.2006199
Serotonin blood test: MedlinePlus Medical Encyclopedia. (2023). https://medlineplus.gov/ency/article/003562.htm#:~:text=Serotonin%20is%20a%20chemical%20produced,bronchial%20tubes%20in%20the%20lungs.
Sheng, J., Liu, S., Wang, Y., Cui, R., & Zhang, X. (2017). The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain. Neural Plasticity, 2017, 1–10. https://doi.org/10.1155/2017/9724371
Sunrise and sunset in Bulgaria. (n.d.). Worlddata.info. https://www.worlddata.info/europe/bulgaria/sunset.php
Sunrise and sunset in Qatar. (n.d.). Worlddata.info. https://www.worlddata.info/asia/qatar/sunset.php
Straub, R. H. (2007). The complex role of estrogens in inflammation. Endocrine Reviews, 28(5), 521–574. https://doi.org/10.1210/er.2007-0001
Terzieva, D. D., Mateva, N. D., & Vladimirova-Kitova, L. G. (2009). Melatonin reference limits at 3:00 AM and 8:00 AM in healthy adults. Clinical Laboratory, 9–10(55), PMID:20090572. https://pubmed.ncbi.nlm.nih.gov/20099572/
Thau, L., Gandhi, J., & Sharma, S. (2023, August 28). Physiology, cortisol. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK538239/
Tordjman, S., Chokron, S., Delorme, R., Charrier, A., Bellissant, E., Jaafari, N., & Fougerou, C. (2017). Melatonin: Pharmacology, functions and therapeutic benefits. Current Neuropharmacology, 15(3), 434–443. https://doi.org/10.2174/1570159x14666161228122115
Ursing, C., Von Bahr, C., Brismar, K., & Röjdmark, S. (2005). Influence of cigarette smoking on melatonin levels in man. European Journal of Clinical Pharmacology, 61(3), 197–201. https://doi.org/10.1007/s00228-005-0908-7
Valencia, L. M. P., He, Y., & Wippert, P. (2024). The changes of blood-based inflammatory biomarkers after non-pharmacologic interventions for chronic low back pain: a systematic review. BMC Musculoskeletal Disorders, 25(1). https://doi.org/10.1186/s12891-024-07289-1
Vasey, C., McBride, J., & Penta, K. (2021). Circadian Rhythm Dysregulation and Restoration: The Role of Melatonin. Nutrients, 13(10), 3480. https://doi.org/10.3390/nu13103480
Williamson, A., & Hoggart, B. (2005). Pain: a review of three commonly used pain rating scales. Journal of Clinical Nursing, 14(7), 798–804. https://doi.org/10.1111/j.1365-2702.2005.01121.x
Whale, K., & Gooberman‐Hill, R. (2022). The importance of sleep for people with chronic pain: Current insights and evidence. JBMR Plus, 6(7). https://doi.org/10.1002/jbm4.10658
Woo, A. K. (2010). Depression and anxiety in pain. Reviews in Pain, 4(1), 8–12. https://doi.org/10.1177/204946371000400103
World Bank Climate Change Knowledge Portal. (2021). http://climateknowledgeportal.worldbank.org/country/qatar/climate-data-historical#:~:text=The%20country%20experiences%20long%20summers,more%20rainfall%20than%20the%20south.
Wyns, A., Hendrix, J., Lahousse, A., De Bruyne, E., Nijs, J., Godderis, L., & Polli, A. (2023). The Biology of Stress Intolerance in Patients with Chronic Pain—State of the Art and Future Directions. Journal of Clinical Medicine, 12(6), 2245. https://doi.org/10.3390/jcm12062245
Xu, X., & Huang, Y. (2020). Objective Pain Assessment: a Key for the Management of Chronic Pain. F1000Research, 9, 35. https://doi.org/10.12688/f1000research.20441.1
Yousef, P., Rosen, J., & Shapiro, C. (2024). Tryptophan and its role in sleep and mood. In Studies in natural products chemistry (pp. 1–14). https://doi.org/10.1016/b978-0-443-15589-5.00001-3
Zhuang, J., Mei, H., Fang, F., & Ma, X. (2022). What is new in Classification, diagnosis and Management of Chronic Musculoskeletal Pain: A Narrative review. Frontiers in Pain Research, 3. https://doi.org/10.3389/fpain.2022.937004

Presenting Author: Linzette D. Morris
Submitting Author: Linzette Morris

Senior Author: Linzette D. Morris

IASP 2026 Global Year theme of Neuropathic Pain: No