Background & Aims
Mounting evidence has revealed sex-specific differences in chronic pain conditions, such as migraines [1], as well as in the mechanisms of pain processing and modulation. The balance and the levels of testosterone and estrogen were reported to affect one’s perception of pain. [2] However, the sex differences in the association between gonadal hormones and pain perception remain to be explored, particularly in healthy individuals. Moreover, continual pain conditions are thought to interfere with pain processing. [3, 4] Therefore, this exploratory study investigated the association between pain perception and salivary testosterone levels in both healthy controls (HCs) and patients with migraines (MIGs). We hypothesized that discernible sex differences would be identified in the association between experimental pain levels and testosterone levels, and that this relationship may be further complicated in MIG.
Methods
Male and female HCs without any pain conditions and MIGs who received a migraine diagnosis based on the International Classification of Headache Disorders, 3rd Edition (ICHD-3)[5] were recruited. The participants sequentially finished a questionnaire battery, saliva sample collection, and pain assessments. The participants completed a series of questionnaires to evaluate their psychosocial profiles, including mood, stress, and sleep quality data. Saliva samples were collected using Salivette Cortisol commercial collection tubes (Sarstedt, Germany), and salivary testosterone levels were analyzed using a commercial enzyme-linked immunosorbent assay kit (Salimetrics 1-2402, Testosterone ELISA Kit). Heat pain thresholds and suprathreshold pain ratings at 45°C (referred to as the pain perception score, PPS) were assessed using Medoc TSA-II NeuroSensory Analyzer (Medoc, Israel). A 30 mm × 30 mm Thermode probe was securely placed on the left ventromedial forearm.
Results
A total of 88 HCs (men: 41, age: 29.9±7.7 years) and 75 MIGs (men: 30, age: 31.1±7.7 years) completed all assessments. A positive correlation between testosterone levels and PPS was identified in the male HCs (r=0.341, P=0.029), whereas a negative correlation was identified in the female HCs (r=?0.407, P=0.005). No such correlations were identified in the MIG group. Subanalysis to control for the menstrual phase and noted no significant differences in testosterone levels between women in the ovulation (n = 17) and nonovulation phases (n = 75; P = 0.912, Mann–Whitney U test). To improve the robustness of our results, we performed a partial correlation analysis between PPS and testosterone levels, controlling for the menstrual phase, and obtained similar results (HC: r = ?0.381, P = 0.009; MIG: r = ?0.034, P = 0.829). The comparison was made between HC and MIG in males and females, respectively. No significant differences were found between groups in both sexes.
Conclusions
This study confirms that a negative relationship is present between PPS and testosterone levels in female HCs, which is in line with the findings of studies that have considered testosterone to be an antinociceptive agent. Our study is the first to demonstrate a sex-specific association between PPS and testosterone levels in HCs. Moreover, this study also revealed that the presence of a chronic pain condition, such as migraine, appears to disrupt this association.
References
1. Stovner LJ, Hagen K, Linde M, Steiner TJ (2022) The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain 23:34. https://doi.org/10.1186/s10194-022-01402-2
2. Vincent K, Tracey I (2008) Hormones and their Interaction with the Pain Experience. Rev Pain 2:20. https://doi.org/10.1177/204946370800200206
3. Baliki MN, Geha PY, Apkarian AV, Chialvo DR (2008) Beyond Feeling: Chronic Pain Hurts the Brain, Disrupting the Default-Mode Network Dynamics. J Neurosci 28:1398–1403. https://doi.org/10.1523/JNEUROSCI.4123-07.2008
4. Mano H, Seymour B (2015) Pain: A Distributed Brain Information Network? PLoS Biol 13:e1002037. https://doi.org/10.1371/journal.pbio.1002037
5. Headache Classification Committee of the International Headache Society (2018) The International Classification of Headache Disorders, 3rd edition. Cephalalgia 38:1–211. https://doi.org/10.1177/0333102417738202
Presenting Author
Li-Ling Hope Pan
Poster Authors
Li-Ling Hope Pan, PhD
PT, Ph.D.
Brain Research Center, National Yang Ming Chiao Tung University
Lead Author
Shih-Pin Chen
MD
Institute of Clinical Medicine, National Yang Ming Chiao Tung University
Lead Author
Yu-Hsiang Ling
MD
College of Medicine, National Yang Ming Chiao Tung University
Lead Author
Yen-Feng Wang
MD
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
Lead Author
Kuan-Lin Lai
MD
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
Lead Author
Hung-Yu Liu
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital
Lead Author
Wei-Ta Chen
MD
Department of Neurology, Keelung Hospital, Ministry of Health and Welfare
Lead Author
William Huang
MD
Department of Urology, Taipei Veterans General Hospital
Lead Author
Gianluca Coppola
MD
Department of Medico?Surgical Sciences and Biotechnologies, Sapienza University of Rome Polo Pont
Lead Author
Rolf-Detlef Treede
Heidelberg University
Lead Author
Shuu-Jiun Wang
PhD
College of Medicine, National Yang Ming Chiao Tung University
Lead Author
Topics
- Mechanisms: Biological-Systems (Physiology/Anatomy)