Search tips
Search criteria 


Logo of headpainSpringerOpen.comSubmit OnlineRegisterThis journalThis article
J Headache Pain. 2008 August; 9(4): 221–224.
Published online 2008 July 2. doi:  10.1007/s10194-008-0047-5
PMCID: PMC3451944

Low urinary 6-sulphatoxymelatonin concentrations in acute migraine


Substantial evidence points to melatonin as playing a role in the regulation of circadian rhythms, sleep, and headache disorders. The objective of the study was to assess 6-sulphatoxymelatonin (aMT6s) levels in a large consecutive series of patients with migraine, comparing with controls. A total of 220 subjects were evaluated—146 had migraine and 74 were control subjects. Urinary samples were collected into the same plastic container since 8:00 p.m. to 8:00 a.m. of the next day (12-h period) and aMT6s was measured with quantitative ELISA technique. Among patients with migraine, 53% presented pain on the day of the urine samples collection. Their urinary aMT6s concentration was significantly lower than in the urine of patients without pain [14.0 ± 7.3 vs. 49.4 ± 19.0; t(143) = −15.1; 95% CI = −40.0 to −30.8; P < 0.001]. There was no significant difference in the aMT6s concentration of patients with migraine without pain on the day of their urine samples collection and controls [49.4 ± 19.0 vs. 42.5 ± 27.9; t(140) = 1.7; 95% CI = −1.2 to 14.8; P = 0.094]. To our knowledge, this is the first study to demonstrate reduction in melatonin levels during attacks in episodic and chronic migraine.

Keywords: Circadian rhythm, Pathophysiology, Melatonin, Migraine, Headache

Full Text

The Full Text of this article is available as a PDF (159K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Blau JN. Migraine pathogenesis: the neural hypothesis reexamined. J Neurol Neurosurg Psychiatry. 1984;47(5):437–442. [PMC free article] [PubMed]
2. Bruyn GW. The biochemistry of migraine. Headache. 1980;20(5):235–246. doi: 10.1111/j.1526-4610.1980.hed2005235.x. [PubMed] [Cross Ref]
3. Silberstein SD. Advances in understanding the pathophysiology of headache. Neurology. 1992;42:6–10. [PubMed]
4. Zurak N. Role of the suprachiasmatic nucleus in the pathogenesis of migraine attacks. Cephalalgia. 1997;17(7):723–728. doi: 10.1046/j.1468-2982.1997.1707723.x. [PubMed] [Cross Ref]
5. Rao NS, Pearce J. Hypothalamic–pituitary–adrenal axis studies in migraine with special reference to insulin sensitivity. Brain. 1971;94(2):289–298. doi: 10.1093/brain/94.2.289. [PubMed] [Cross Ref]
6. Kaube H, Goadsby PJ. Anti-migraine compounds fail to modulate the propagation of cortical spreading depression in the cat. Eur Neurol. 1994;34(1):30–35. doi: 10.1159/000117004. [PubMed] [Cross Ref]
7. Wever RA. The circadian system of man: results of experiments under temporal isolation. Berlin: Springer; 1979.
8. Dodick DW, et al. Clinical, anatomical, and physiologic relationship between sleep and headache. Headache. 2003;43(3):282–292. doi: 10.1046/j.1526-4610.2003.03055.x. [PubMed] [Cross Ref]
9. Bojkowski CJ, Arendt J. Factors influencing urinary 6-sulphatoxymelatonin, a major melatonin metabolite, in normal human subjects. Clin Endocrinol (Oxf) 1990;33(4):435–444. doi: 10.1111/j.1365-2265.1990.tb03882.x. [PubMed] [Cross Ref]
10. Peres MF. Melatonin, the pineal gland and their implications for headache disorders. Cephalalgia. 2005;25(6):403–411. doi: 10.1111/j.1468-2982.2005.00889.x. [PubMed] [Cross Ref]
11. Markey SP, et al. The correlation between human plasma melatonin levels and urinary 6-hydroxymelatonin excretion. Clin Chim Acta. 1985;150(3):221–225. doi: 10.1016/0009-8981(85)90247-5. [PubMed] [Cross Ref]
12. Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336(3):186–195. doi: 10.1056/NEJM199701163360306. [PubMed] [Cross Ref]
13. Claustrat B, et al. Nocturnal plasma melatonin levels in migraine: a preliminary report. Headache. 1989;29(4):242–245. doi: 10.1111/j.1526-4610.1989.hed22904242.x. [PubMed] [Cross Ref]
14. Brun J, et al. Nocturnal melatonin excretion is decreased in patients with migraine without aura attacks associated with menses. Cephalalgia. 1995;15(2):136–139. doi: 10.1046/j.1468-2982.1995.015002136.x. [PubMed] [Cross Ref]
15. Murialdo G, et al. Urinary melatonin excretion throughout the ovarian cycle in menstrually related migraine. Cephalalgia. 1994;14(3):205–209. doi: 10.1046/j.1468-2982.1994.014003205.x. [PubMed] [Cross Ref]
16. Claustrat B, et al. Melatonin secretion is supersensitive to light in migraine. Cephalalgia. 2004;24(2):128–133. doi: 10.1111/j.1468-2982.2004.00645.x. [PubMed] [Cross Ref]
17. Salvesen R, Bekkelund SI. Migraine, as compared to other headaches, is worse during midnight-sun summer than during polar night. A questionnaire study in an Arctic population. Headache. 2000;40(10):824–829. doi: 10.1046/j.1526-4610.2000.00149.x. [PubMed] [Cross Ref]
18. The International Classification of Headache Disorders (2004) 2nd edn. Cephalalgia 24(suppl 1):9–160 [PubMed]
19. Bojkowski CJ, Arendt J. Annual changes in 6-sulphatoxymelatonin excretion in man. Acta Endocrinol (Copenh) 1988;117(4):470–476. [PubMed]
20. Peres MF, et al. Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry. 2001;71(6):747–751. doi: 10.1136/jnnp.71.6.747. [PMC free article] [PubMed] [Cross Ref]

Articles from The Journal of Headache and Pain are provided here courtesy of Springer