Pain sensitivity in men who have never experienced a headache: an observer blinded case control study

Isa Amalie Olofsson, Jeppe Hvedstrup, Katrine Falkenberg, Mona Ameri Chalmer, Henrik Winther Schytz, Miguel Benjamin Pedersen, Henrik Ullum, Ole Birger Pedersen, Jes Olesen, Thomas Folkmann Hansen, Isa Amalie Olofsson, Jeppe Hvedstrup, Katrine Falkenberg, Mona Ameri Chalmer, Henrik Winther Schytz, Miguel Benjamin Pedersen, Henrik Ullum, Ole Birger Pedersen, Jes Olesen, Thomas Folkmann Hansen

Abstract

Background: Headache affects 90-99% of the population. Based on the question "Do you think that you never ever in your whole life have had a headache?" 4% of the population say that they have never experienced a headache. The rarity of never having had a headache suggests that distinct biological and environmental factors may be at play. We hypothesized that people who have never experienced a headache had a lower general pain sensitivity than controls.

Methods: We included 99 male participants, 47 headache free participants and 52 controls, in an observer blinded nested case-control study. We investigated cold pain threshold and heat pain threshold using a standardized quantitative sensory testing protocol, pericranial tenderness with total tenderness score and pain tolerance with the cold pressor test. Differences between the two groups were assessed with the unpaired Student's t-test or Mann-Whitney U test as appropriate.

Results: There was no difference in age, weight or mean arterial pressure between headache free participants and controls. We found no difference in pain detection threshold, pericranial tenderness or pain tolerance between headache free participants and controls.

Conclusion: Our study clearly shows that freedom from headache is not caused by a lower general pain sensitivity. The results support the hypothesis that headache is caused by specific mechanisms, which are present in the primary headache disorders, rather than by a decreased general sensitivity to painful stimuli.

Trial registration: Registered at ClinicalTrials.gov ( NCT04217616 ), 3rd January 2020, retrospectively registered.

Keywords: Cold pressor test; Never had headache; Never headache; Pain sensitivity; Pain threshold; Quantitative sensory testing; Total tenderness score.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Inclusion of participants. Flowchart illustrating inclusion and exclusion of participants for the study
Fig. 2
Fig. 2
Distribution of total tenderness score. Comparison of the distribution of total tenderness score in headache free participants and controls
Fig. 3
Fig. 3
Pain tolerance. Proportion of headache free participants and controls who stopped the cold pressor test over time

References

    1. Rasmussen BK, Jensen R, Schroll M, Olesen J. Epidemiology of headache in a general population-a prevalence study. J Clin Epidemiol. 1991;44(11):1147–1157. doi: 10.1016/0895-4356(91)90147-2.
    1. Boardman HF, Thomas E, Croft PR, Millson DS. Epidemiology of headache in an English district. Cephalalgia. 2003;23(2):129–137. doi: 10.1046/j.1468-2982.2003.00468.x.
    1. Nikiforow R. Headache in a random sample of 200 persons: a clinical study of a population in northern Finland. Cephalalgia. 1981;1(2):99–107. doi: 10.1111/j.1468-2982.1981.tb00016.x.
    1. Le H, Tfelt-Hansen P, Skytthe A, et al. Increase in self-reported migraine prevalence in the Danish adult population: a prospective longitudinal population-based study. BMJ Open. 2012;2(4):e000962. doi: 10.1136/bmjopen-2012-000962.
    1. Lyngberg AC, Rasmussen BK, Jørgensen T, Jensen R. Has the prevalence of migraine and tension-type headache changed over a 12-year period? A Danish population survey. Eur J Epidemiol. 2005;20(3):243–249. doi: 10.1007/s10654-004-6519-2.
    1. Olofsson IA, Kogelman L, Rasmussen A, Erikstrup C, Sørensen E, Paarup HM, Hjalmgrim H, Banasik K, Nielsen KR, Burgdorf KS, Pedersen OBV, Ullum H, Olesen J, Hansen TF. Prevalence and socio-demographic characteristics of persons who have never had a headache among healthy voluntary blood donors – a population-based study. Cephalalgia. 2020;40(10):1055–1062. doi: 10.1177/0333102420920653.
    1. Langemark M, Jensen K, Jensen TS, Olesen J. Pressure pain thresholds and thermal nociceptive thresholds in chronic tension-type headache. Pain. 1989;38(2):203–210. doi: 10.1016/0304-3959(89)90239-X.
    1. Jensen R, Bendtsen L, Olesen J. Muscular factors are of importance in tension-type headache. Headache J Head Face Pain. 1998;38(1):10–17. doi: 10.1046/j.1526-4610.1998.3801010.x.
    1. Uthaikhup S, Sterling M, Jull G. Widespread sensory hypersensitivity is not a feature of chronic headache in elders. Clin J Pain. 2009;25(8):699–704. doi: 10.1097/AJP.0B013E3181A38F88.
    1. Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH. An association between migraine and cutaneous allodynia. Ann Neurol. 2000;47(5):614–624. doi: 10.1002/1531-8249,.
    1. Engstrøm M, Hagen K, Bjørk MH, Stovner LJ, Gravdahl GB, Stjern M, Sand T. Sleep quality, arousal and pain thresholds in migraineurs: a blinded controlled polysomnographic study. J Headache Pain. 2013;14(1):12. doi: 10.1186/1129-2377-14-12.
    1. Schwedt T, Krauss M, Frey K, Gereau R. Episodic and chronic migraineurs are hypersensitive to thermal stimuli between migraine attacks. Cephalalgia. 2011;31(1):6–12. doi: 10.1177/0333102410365108.
    1. Uglem M, Omland PM, Nilsen KB, Tronvik E, Stovner LJ, Hagen K, Linde M, Sand T. Does pain sensitivity change by migraine phase? A blinded longitudinal study. Cephalalgia. 2017;37(14):1337–1349. doi: 10.1177/0333102416679955.
    1. Teepker M, Kunz M, Peters M, Kundermann B, Schepelmann K, Lautenbacher S. Endogenous pain inhibition during menstrual cycle in migraine. Eur J Pain. 2014;18(7):989–998. doi: 10.1002/j.1532-2149.2013.00444.x.
    1. Schwedt TJ, Chong CD. Correlations between brain cortical thickness and cutaneous pain thresholds are atypical in adults with migraine. PLoS One. 2014;9(6):e99791. doi: 10.1371/JOURNAL.PONE.0099791.
    1. Beese LC, Putzer D, Osada N, Evers S, Marziniak M. Contact heat evoked potentials and habituation measured interictally in migraineurs. J Headache Pain. 2015;161(16):1–12. doi: 10.1186/1129-2377-16-1.
    1. Weissman-Fogel I, Sprecher E, Granovsky Y, Yarnitsky D. Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons. Pain. 2003;104(3):693–700. doi: 10.1016/S0304-3959(03)00159-3.
    1. Ashina S, Babenko L, Jensen R, Ashina M, Magerl W, Bendtsen L. Increased muscular and cutaneous pain sensitivity in cephalic region in patients with chronic tension-type headache. Eur J Neurol. 2005;12(7):543–549. doi: 10.1111/j.1468-1331.2005.01023.x.
    1. Jensen R, Rasmussen BK, Pedersen B, Olesen J. Muscle tenderness and pressure pain thresholds in headache. A population study. Pain. 1993;52(2):193–199. doi: 10.1016/0304-3959(93)90131-8.
    1. Aaseth K, Grande RB, Lundqvist C, Russell MB. Pericranial tenderness in chronic tension-type headache: the Akershus population-based study of chronic headache. J Headache Pain. 2014;15(1):58. doi: 10.1186/1129-2377-15-58.
    1. Hvedstrup J, Kolding LT, Younis S, Ashina M, Schytz HW. Ictal neck pain investigated in the interictal state – a search for the origin of pain. Cephalalgia. 2020;40(6):614–624. doi: 10.1177/0333102419896369.
    1. Jensen K, Tuxen C, Olesen J. Pericranial muscle tenderness and pressure-pain threshold in the temporal region during common migraine. Pain. 1988;35(1):65–70. doi: 10.1016/0304-3959(88)90277-1.
    1. Cathcart S, Winefield AH, Lushington K, Rolan P. Effect of mental stress on cold pain in chronic tension-type headache sufferers. J Headache Pain. 2009;10(5):367–373. doi: 10.1007/S10194-009-0131-5.
    1. Hassinger H, Semenchuk E, O’Brien W. Appraisal and coping responses to pain and stress in migraine headache sufferers. J Behav Med. 1999;22(4):327–340. doi: 10.1023/A:1018722002393.
    1. Sandrini G, Rossi P, Milanov I, Serrao M, Cecchini AP, Nappi G. Abnormal modulatory influence of diffuse noxious inhibitory controls in migraine and chronic tension-type headache patients. Cephalalgia. 2006;26(7):782–789. doi: 10.1111/j.1468-2982.2006.01130.x.
    1. Bishop KL, Holm JE, Borowiak DM, Wilson BA. Perceptions of pain in women with headache: a laboratory investigation of the influence of pain-related anxiety and fear. Headache. 2001;41(5):494–499. doi: 10.1046/j.1526-4610.2001.01087.x.
    1. Eren OE, Ruscheweyh R, Schankin C, Schöberl F, Straube A. The cold pressor test in interictal migraine patients - different parasympathetic pupillary response indicates dysbalance of the cranial autonomic nervous system. BMC Neurol. 2018;18(1):1–9. doi: 10.1186/s12883-018-1043-2.
    1. Pedersen OB, Erikstrup C, Kotzé SR, Sørensen E, Petersen MS, Grau K, Ullum H. The Danish blood donor study: a large, prospective cohort and biobank for medical research. Vox Sang. 2012;102(3):271–271. doi: 10.1111/j.1423-0410.2011.01553.x.
    1. Burgdorf KS, Simonsen J, Sundby A, Rostgaard K, Pedersen OB, Sørensen E, Nielsen KR, Bruun MT, Frisch M, Edgren G, Erikstrup C, Hjalgrim H, Ullum H. Socio-demographic characteristics of Danish blood donors. PLoS One. 2017;12(2):e0169112. doi: 10.1371/journal.pone.0169112.
    1. Burgdorf KS, Felsted N, Mikkelsen S, Nielsen MH, Thørner LW, Pedersen OB, Sørensen E, Nielsen KR, Bruun MT, Werge T, Erikstrup C, Hansen T, Ullum H. Digital questionnaire platform in the Danish blood donor study. Comput Methods Prog Biomed. 2016;135:101–104. doi: 10.1016/j.cmpb.2016.07.023.
    1. e-Boks. . Accessed 7 Apr 2021
    1. World Medical Association World Medical Association declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA – J Am Med Assoc. 2013;310:2191–2194. doi: 10.1001/jama.2013.281053.
    1. Rolke R, Baron R, Maier C, et al (2006) Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 123(3):231–243. 10.1016/j.pain.2006.01.041
    1. Rolke R, Magerl W, Campbell KA, Schalber C, Caspari S, Birklein F, Treede RD. Quantitative sensory testing: a comprehensive protocol for clinical trials. Eur J Pain. 2006;10(1):77–88. doi: 10.1016/j.ejpain.2005.02.003.
    1. Langemark M, Olesen J. Pericranial tenderness in tension headache. A blind, controlled study. Cephalalgia. 1987;7(4):249–255. doi: 10.1046/j.1468-2982.1987.0704249.x.
    1. Bendtsen L, Jensen R, Jensen NK, Olesen J. Pressure-controlled palpation: a new technique which increases the reliability of manual palpation. Cephalalgia. 1995;15(3):205–210. doi: 10.1046/j.1468-2982.1995.015003205.x.
    1. Bendtsen L, Jensen R, Jensen NK, Olesen J. Muscle palpation with controlled finger pressure: new equipment for the study of tender myofascial tissues. Pain. 1994;59(2):235–239. doi: 10.1016/0304-3959(94)90076-0.
    1. R Core Team . R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2019.
    1. Lous I, Olesen J. Evaluation of pericranial tenderness and oral function in patients with common migraine, muscle contraction headache and ‘combination headache’. Pain. 1982;12(4):385–393. doi: 10.1016/0304-3959(82)90183-X.
    1. Schmidt-Hansen PT, Svensson P, Bendtsen L, Graven-Nielsen T, Bach FW. Increased muscle pain sensitivity in patients with tension-type headache. Pain. 2007;129(1):113–121. doi: 10.1016/J.PAIN.2006.09.037.
    1. Exposto FG, Bendixen KH, Ernberg M, Bach FW, Svensson P. Characterization and predictive mechanisms of experimentally induced tension-type headache. Cephalalgia. 2019;39(10):1207–1218. doi: 10.1177/0333102419840779.
    1. Johansen A, Schirmer H, Stubhaug A, Nielsen CS. Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: comorbid pain matters. Pain. 2014;155(2):341–348. doi: 10.1016/j.pain.2013.10.013.
    1. Pud D, Eisenberg E, Sprecher E, Rogowski Z, Yarnitsky D. The tridimensional personality theory and pain: harm avoidance and reward dependence traits correlate with pain perception in healthy volunteers. Eur J Pain. 2004;8(1):31–38. doi: 10.1016/S1090-3801(03)00065-X.
    1. Fillingim RB, King CD, Ribeiro-Dasilva MC, Rahim-Williams B, Riley JL., III Sex, gender, and pain: a review of recent clinical and experimental findings. J Pain. 2009;10(5):447–485. doi: 10.1016/j.jpain.2008.12.001.
    1. Peng KP, May A. Migraine understood as a sensory threshold disease. Pain. 2019;160(7):1494–1501. doi: 10.1097/j.pain.0000000000001531.

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