Skip to main content

Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache


The goal of this study was to explore the relationship between indicators of sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) activity and stress-induced head and shoulder-neck pain in patients with migraine or tension-type headache (TTH). We measured noradrenaline, adrenaline and cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16 TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 30 min of relaxation. Migraine patients had lower noradrenaline levels in blood platelets compared to controls. Pain responses correlated negatively with noradrenaline levels, and pain recovery correlated negatively with the cortisol change in migraineurs. TTH patients maintained cortisol secretion during the cognitive stress as opposed to the normal circadian decrease seen in controls and migraineurs. There may therefore be abnormal activation of the HPA axis in patients with TTH when coping with mental stress, but no association was found between pain and cortisol. A relationship between HPA activity and stress in TTH patients has to our knowledge not been reported before. In migraine, on the other hand, both sympathoneural activation and HPA activation seem to be linked to stress-induced muscle pain and recovery from pain respectively. The present study suggests that migraineurs and TTH patients cope differently with low-grade cognitive stress.


  1. 1.

    Martin PR, Soon K (1993) The relationship between perceived stress, social support and chronic headaches. Headache 33:307–314, 1:STN:280:DyaK3szlt1aqtQ%3D%3D, 8349473

    Article  CAS  PubMed  Google Scholar 

  2. 2.

    Spierings EL, Ranke AH, Honkoop PC (2001) Precipitating and aggravating factors of migraine versus tension-type headache. Headache 41:554–558, 1:STN:280:DC%2BD38%2FhvFKnsA%3D%3D, 11437890

    Article  CAS  PubMed  Google Scholar 

  3. 3.

    Wacogne C, Lacoste J, Guillibert E, Hugues F, Le Jeunne C (2003) Stress, anxiety, depression and migraine. Cephalalgia 23:451–455, 1:STN:280:DC%2BD3szjslyktA%3D%3D, 12807524

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Zivadinov R, Willheim K, Sepic-Grahovac D et al (2003) Migraine and tension-type headache in Croatia: a population-based survey of precipitating factors. Cephalalgia 23:336–343, 10.1046/j.1468-2982.2003.00544.x, 1:STN:280:DC%2BD3s3ls1emtw%3D%3D, 12780762

    Article  CAS  PubMed  Google Scholar 

  5. 5.

    Eriksen HR, Ursin H (2002) Sensitization and subjective health complaints. Scand J Psychol 43:189–196, 12004958

    Article  PubMed  Google Scholar 

  6. 6.

    McEwen BS (1998) Protective and damaging effects of stress mediators. N Engl J Med 338:171–179, 10.1056/NEJM199801153380307, 1:CAS:528:DyaK1cXmsVKlsw%3D%3D, 9428819

    Article  CAS  PubMed  Google Scholar 

  7. 7.

    Jensen R (1999) Pathophysiological mechanisms of tension-type headache: a review of epidemiological and experimental studies. Cephalalgia 19:602–621, 10.1046/j.1468-2982.1999.019006602.x, 1:STN:280:DyaK1MznslKmug%3D%3D, 10448549

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Jensen R (1996) Mechanisms of spontaneous tension-type headaches: an analysis of tenderness, pain thresholds and EMG. Pain 64:251–256, 1:STN:280:DyaK28zgtlOksQ%3D%3D, 8740601

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Bendtsen L (2003) Central and peripheral sensitization in tension-type headache. Curr Pain Headache Rep 7:460–465, 14604505, 10.1007/s11916-003-0062-9

    Article  PubMed  Google Scholar 

  10. 10.

    Burstein R (2001) Deconstructing migraine headache into peripheral and central sensitization. Pain 89:107–110, 1:STN:280:DC%2BD3M3ksFCnsQ%3D%3D, 11166465

    Article  CAS  PubMed  Google Scholar 

  11. 11.

    Goadsby PJ (2005) Migraine, allodynia, sensitisation and all of that. Eur Neurol 53[Suppl 1]:10–16, 10.1159/000085060, 15920332

    Article  PubMed  Google Scholar 

  12. 12.

    Wallin BG, Sundlof G, Eriksson BM, Dominiak P, Grobecker H, Lindblad LE (1981) Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man. Acta Physiol Scand 111:69–73, 10.1111/j.1748-1716.1981.tb06706.x, 1:CAS:528:DyaL3MXotFCjtA%3D%3D, 7223453

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89, 10.1210/er.21.1.55, 1:CAS:528:DC%2BD3cXhs12hu78%3D, 10696570

    CAS  PubMed  Google Scholar 

  14. 14.

    De Kloet ER (2004) Hormones and the stressed brain. Ann N Y Acad Sci 1018:1–15, 10.1196/annals.1296.001, 15240347

    Article  PubMed  Google Scholar 

  15. 15.

    Cortelli P, de Carolis P, Sturani A et al (1986) Cardiovascular and biochemical assessment in migraine patients submitted to tilt test. Functional Neurology 1:285–290, 1:STN:280:DyaL2s3nslGqsQ%3D%3D, 3609861

    CAS  PubMed  Google Scholar 

  16. 16.

    Mikamo K, Takeshima T, Takahashi K (1989) Cardiovascular sympathetic hypofunction in muscle contraction headache and migraine. Headache 29:86–89, 10.1111/j.1526-4610.1989.hed2902086.x, 1:STN:280:DyaL1M3htlelsg%3D%3D, 2708041

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    D’Andrea G, Welch KM, Nagel-Leiby S, Grunfeld S, Joseph R (1989) Platelet catecholamines in migraine. Cephalalgia 9:3–5, 10.1046/j.1468-2982.1989.0901003.x, 2706673

    Article  PubMed  Google Scholar 

  18. 18.

    Stronks DL, Tulen JH, Verheij R et al (1998) Serotonergic, catecholaminergic, and cardiovascular reactions to mental stress in female migraine patients. A controlled study. Headache 38:270–280, 10.1046/j.1526-4610.1998.3804270.x, 1:STN:280:DyaK1c3lvVagsg%3D%3D, 9595866

    Article  CAS  PubMed  Google Scholar 

  19. 19.

    Castillo J, Martinez F, Leira R, Lema M, Noya M (1994) Plasma monoamines in tension-type headache. Headache 34:531–535, 10.1111/j.1526-4610.1994.hed3409531.x, 1:STN:280:DyaK2M%2FpsFKgsA%3D%3D, 8002328

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Leistad RB, Sand T, Westgaard R, Nilsen KB, Stovner LJ (2006) Stress-induced pain and muscle activity in patients with migraine and tension-type headache. Cephalalgia 26:64–73, 10.1111/j.1468-2982.2005.00997.x, 1:STN:280:DC%2BD28%2FhtVCmuw%3D%3D, 16396668

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Nilsen KB, Westgaard RH, Stovner LJ, Helde G, Rø M, Sand TH (2006) Pain induced by low-grade stress in patients with fibromyalgia and chronic shoulder/neck pain, relation to surface electromyography. Eur J Pain 10:615–627, 10.1016/j.ejpain.2005.10.001, 1:STN:280:DC%2BD28rhtV2htA%3D%3D, 16300974

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Westgaard RH, Bjørklund R (1987) Generation of muscle tension additional to postural muscle load. Ergonomics 30:911–923, 1:STN:280:DyaL2szgsVWlsw%3D%3D, 3622473

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Leone M, Biffi M, Leoni F, Bussone G (1994) Leukocyte subsets and cortisol serum levels in patients with migraine without aura and chronic tension-type headache. Cephalalgia 14:139–142, 10.1046/j.1468-2982.1994.1402139.x, 1:STN:280:DyaK2czktVKqsQ%3D%3D, 8062352

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Peres MF, Sanchez del Rio M, Seabra ML et al (2001) Hypothalamic involvement in chronic migraine. J Neurol Neurosurg Psychiatry 71:747–751, 10.1136/jnnp.71.6.747, 1:STN:280:DC%2BD3MnnslWhtg%3D%3D, 11723194

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  25. 25.

    Headache Classification Committee of the International Headache Society. (1988) Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. Cephalalgia 7[Suppl 7]:1–96

    Google Scholar 

  26. 26.

    Smith CC, Curtis LD, Delamothe AP, Prichard BN, Betteridge DJ (1985) The distribution of catecholamines between platelets and plasma in normal human subjects. Clin Sci (Colch) 69:1–6, 1:CAS:528:DyaL2MXktlaks7s%3D

    Article  CAS  Google Scholar 

  27. 27.

    Candito M, Bree F, Krstulovic AM (1996) Plasma catecholamine assays: calibration with spiked plasma versus aqueous solutions. Biomed Chromatogr 10:40–42, 1:CAS:528:DyaK28XntVeisQ%3D%3D, 8821871

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Pintar JE, Breakefield XO (1982) Monoamine oxidase (MAO) activity as a determinant in human neurophysiology. Behav Genet 12:53–68, 1:STN:280:DyaL383jtFWisA%3D%3D, 6284115

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Gotoh F, Komatsumoto S, Araki N, Gomi S (1984) Noradrenergic nervous activity in migraine. Arch Neurol 41:951–955, 1:STN:280:DyaL2czgs1Ogsg%3D%3D, 6477230

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    Martinez F, Castillo J, Pardo J, Lema M, Noya M (1993) Catecholamne levels in plasma and CSF in migraine. J Neurol Neurosurg Psychiatry 56:1119–1121, 1:STN:280:DyaK2c%2FhsFSqsw%3D%3D, 8410012

    PubMed Central  Article  CAS  PubMed  Google Scholar 

  31. 31.

    D’Andrea G, Welch KM, Grunfeld S, Joseph R, Nagel-Leiby S (1989) Platelet norepinephrine and serotonin balance in migraine. Headache 29:657–659, 10.1111/j.1526-4610.1989.hed2910657.x, 2613514

    Article  PubMed  Google Scholar 

  32. 32.

    Takeshima T, Takao Y, Urakami K, Nishikawa S, Takahashi K (1989) Muscle contraction headache and migraine. Platelet activation and plasma norepinephrine during the cold pressor test. Cephalalgia 9:7–13, 10.1046/j.1468-2982.1989.0901007.x, 1:STN:280:DyaL1M3gvVOksg%3D%3D, 2706677

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Carstensen E, Yudkin JS (1994) Platelet catecholamine concentrations after short-term stress in normal subjects. Clin Sci (Colch) 86:35–41

    Article  CAS  Google Scholar 

  34. 34.

    Martignoni E, Facchinetti F, Rossi F, Sances G, Genazzani AR, Nappi G (1989) Neuroendocrine evidence of deranged noradrenergic activity in chronic migraine. Psychoneuroendocrinology 14:357–363, 10.1016/0306-4530(89)90005-X, 1:CAS:528:DyaK3cXls1Gi, 2554358

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Turton MB, Deegan T (1974) Circadian variations of plasma catecholamine, cortisol and immunoreactive insulin concentrations in supine subjects. Clin Chim Acta 55:389–397, 10.1016/0009-8981(74)90014-X, 1:CAS:528:DyaE2MXhsVGgsw%3D%3D, 4412449

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Barden N (2004) Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression. J Psychiatry Neurosci 29:185–193, 15173895

    PubMed Central  PubMed  Google Scholar 

  37. 37.

    Dickerson SS, Kemeny ME (2004) Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull 130:355–391, 10.1037/0033-2909.130.3.355, 15122924

    Article  PubMed  Google Scholar 

  38. 38.

    Chrousos GP, Torpy DJ, Gold PW (1998) Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 129:229–240, 1:STN:280:DyaK1czkvVaqug%3D%3D, 9696732

    Article  CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Rune Bang Leistad.

Rights and permissions

Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( ), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Reprints and Permissions

About this article

Cite this article

Leistad, R.B., Stovner, L.J., White, L.R. et al. Noradrenaline and cortisol changes in response to low-grade cognitive stress differ in migraine and tension-type headache. J Headache Pain 8, 157–166 (2007).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Catecholamines
  • Cortisol
  • Migraine
  • Tension-type headache
  • Stress