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Salivary Cortisol and Cold Pain Sensitivity in Female Twins

  • Original Article
  • Published:
Annals of Behavioral Medicine

Abstract

Background

There is a dearth of knowledge about the link between cortisol and pain sensitivity.

Purpose

We examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding.

Methods

Three-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations.

Results

Lower diurnal variation of cortisol was associated with higher pain ratings at threshold (p = 0.02) and tolerance (p < 0.01). The relationship of diurnal variation with pain ratings at threshold and tolerance was minimally influenced by familial factors (i.e., genetics and common environment).

Conclusions

Understanding the genetic and non-genetic mechanisms underlying the link between HPA axis dysregulation and pain sensitivity may help to prevent chronic pain development and maintenance.

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References

  1. Turk DC, Okifuji A. Psychological factors in chronic pain: Evolution and revolution. J Consult Clin Psych. 2002; 70: 678-690.

    Article  Google Scholar 

  2. Stewart WF, Ricci JA, Chee E, Morganstein D, Lipton R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003; 290: 2443-2454.

    Article  PubMed  CAS  Google Scholar 

  3. Gatchel RJ, Peng YB, Peters ML, Fuchs PN, Turk DC. The biopsychosocial approach to chronic pain: Scientific advances and future directions. Psychol Bull. 2007; 133: 581-624.

    Article  PubMed  Google Scholar 

  4. Hassett AL, Clauw DJ. Does psychological stress cause chronic pain? Psychiatr Clin N Am. 2011; 34: 579-594.

    Article  Google Scholar 

  5. Kudielka BM, Wüst S. Human models in acute and chronic stress: Assessing determinants of individual hypothalamus–pituitary–adrenal axis activity and reactivity. Stress. 2010; 13: 1-14.

    Article  PubMed  Google Scholar 

  6. Miller GE, Chen E, Zhou ES. If it goes up, must it come down? Chronic stress and the hypothalamic–pituitary–adrenocortical axis in humans. Psychol Bull. 2007; 133: 25-45.

    Article  PubMed  Google Scholar 

  7. Fries E, Dettenborn L, Kirschbaum C. The cortisol awakening response (CAR): Facts and future directions. Int J Psychophysiol. 2009; 72: 67-73.

    Article  PubMed  Google Scholar 

  8. Fries E, Hesse J, Hellhammer J, Hellhammer DH. A new view on hypocortisolism. Psychoneuroendocrinology. 2005; 30: 1010-1016.

    Article  PubMed  CAS  Google Scholar 

  9. Cohen S, Janicki-Deverts D, Miller GE. Psychological stress and disease. JAMA. 2007; 298: 1685-1687.

    Article  PubMed  CAS  Google Scholar 

  10. Maletic V, Raison CL. Neurobiology of depression, fibromyalgia and neuropathic pain. Front Biosci. 2009; 14: 5291-5338.

    Article  CAS  Google Scholar 

  11. Raison CL, Miller AH. When not enough is yoo much: The role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatr. 2003; 160: 1554-1565.

    Article  PubMed  Google Scholar 

  12. Riva R, Mork PJ, Westgaard RH, Magne R, Lundberg U. Fibromyalgia syndrome is associated with hypocortisolism. Int J Behav Med. 2010; 17: 223-233.

    Article  PubMed  Google Scholar 

  13. Van Houdenhove B, Luyten P, Egle UT. Stress as a key concept in chronic widespread pain and fatigue disorders. J Musculoskelet Pain. 2009; 17: 390-399.

    Article  Google Scholar 

  14. McBeth J, Chiu YH, Silman AJ, et al. Hypothalamic–pituitary–adrenal stress axis function and the relationship with chronic widespread pain and its antecedents. Arthritis Res Ther. 2005; 7: R992-R1000.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  15. McBeth J, Silman AJ, Gupta A, et al. Moderation of psychosocial risk factors through dysfunction of the hypothalamic–pituitary–adrenal stress axis in the onset of chronic widespread musculoskeletal pain: Findings of a population-based prospective cohort study. Arthritis Rheum. 2007; 56: 360-371.

    Article  PubMed  CAS  Google Scholar 

  16. McLean SA, Williams DA, Harris RE, et al. Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia. Arthritis Rheum. 2005; 52: 3660-3669.

    Article  PubMed  CAS  Google Scholar 

  17. Bonifazi M, Suman AL, Cambiaggi C, et al. Changes in salivary cortisol and corticosteroid receptor-alpha mRNA expression following a 3-week multidisciplinary treatment program in patients with fibromyalgia. Psychoneuroendocrinology. 2006; 31: 1076-1086.

    Article  PubMed  CAS  Google Scholar 

  18. Park JY, Ahn RS. Hypothalamic–pituitary–adrenal axis function in patients with complex regional pain syndrome type 1. Psychoneuroendocrinology. 2012; 37: 1557-1568.

    Article  PubMed  CAS  Google Scholar 

  19. Johansson AC, Gunnarsson LG, Linton SJ, et al. Pain, disability and coping reflected in the diurnal cortisol variability in patients scheduled for lumbar disc surgery. Eur J Pain. 2008; 12: 633-640.

    Article  PubMed  CAS  Google Scholar 

  20. Mayes LA, McGuire L, Page GG, et al. The association of the cortisol awakening response with experimental pain ratings. Psychoneuroendocrinology. 2009; 34: 1247-1251.

    Article  PubMed Central  CAS  Google Scholar 

  21. Kuehl LK, Michaux GP, Richter S, Schächinger H, Anton F. Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism. Pain. 2010; 149: 539-546.

    Article  PubMed  CAS  Google Scholar 

  22. Dadabhoy D, Crofford LJ, Spaeth M, Russell IJ, Clauw DJ. Biology and therapy of fibromyalgia: Evidence-based biomarkers for fibromyalgia syndrome. Arthritis Res Ther. 2008; 10: 211.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Edwards RR. Individual differences in endogenous pain modulation as a risk factor for chronic pain. Neurology. 2005; 65: 437-443.

    Article  PubMed  Google Scholar 

  24. Ouellet-Morin I, Dionne G, Perusse D, et al. Daytime cortisol secretion in 6-month-old twins: Genetic and environmental contributions as a function of early familial adversity. Biol Psychiatry. 2009; 65: 409-416.

    Article  PubMed  CAS  Google Scholar 

  25. Kim H, Mittal DP, Iadarola MJ, Dionne RA: Genetic predictors for acute experimental cold and heat pain sensitivity in humans. J Med Genet. 2006; 43.

  26. Holliday KL, Nicholl BI, Macfarlane GJ, et al. Genetic variation in the hypothalamic-pituitary-adrenal stress axis influences susceptibility to musculoskeletal pain: Results from the EPIFUND study. Ann Rheum Dis. 2010; 69: 556-560.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Afari N, Noonan C, Goldberg J, et al. University of Washington Twin Registry: Construction and characteristics of a community-based twin registry. Twin Res Hum Genet. 2006; 9: 1023-1029.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Strachan E, Hunt C, Afari N, et al.: University of Washington Twin Registry: Poised for the Next Generation of Twin Research. Twin Res Human Genet: Off J Int Soc Twin Stud. 2012;1–8.

  29. Afari N, Mostoufi S, Noonan C, et al. C-reactive protein and pain sensitivity: Findings from female twins. Ann Behav Med. 2011; 42: 277-283.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Eisen S, Neuman R, Goldberg J, Rice J, True W. Determining zygosity in the Vietnam Era Twin Registry: An approach using questionnaires. Clin Genet. 1989; 35: 423-432.

    Article  PubMed  CAS  Google Scholar 

  31. Magnus P, Berg K, Nance WE. Predicting zygosity in Norwegian twin pairs born 1915–1960. Clin Genet. 1983; 24: 103-112.

    Article  PubMed  CAS  Google Scholar 

  32. Reed T, Plassman BL, Tanner CM, et al. Verification of self-report of zygosity determined via DNA testing in a subset of the NAS-NRC twin registry 40 years later. Twin Res Hum Genet. 2005; 8: 362-367.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Torgersen S. The determination of twin zygosity by means of a mailed questionnaire. Acta Genet Med Gemellol (Roma). 1979; 28: 225-236.

    CAS  Google Scholar 

  34. Nicolson NA. Measurement of cortisol. In: Gallo LC, Luecken LJ, eds. Handbook of Physiological Research Methods in Health Psychology. Thousand Oaks, CA: Sage Publications, Inc.; 2008: 37-74.

    Chapter  Google Scholar 

  35. Turk DC, Meichenbaum D, Genest M. Pain and behavioral medicine: A cognitive-behavioral perspective. New York: Guilford; 1983.

    Google Scholar 

  36. Begg MD, Parides MK. Separation of individual-level and cluster-level covariate effects in regression analysis of correlated data. Stat Med. 2003; 22: 2591-2602.

    Article  PubMed  Google Scholar 

  37. Fillingim RB, Edwards RR, Powell T. The relationship of sex and clinical pain to experimental pain responses. Pain. 1999; 83: 419-425.

    Article  PubMed  CAS  Google Scholar 

  38. Stone AA, Schwartz JE, Smyth J, et al. Individual differences in the diurnal cycle of salivary free cortisol: A replication of flattened cycles for some individuals. Psychoneuroendocrinology. 2001; 26: 295-306.

    Article  PubMed  CAS  Google Scholar 

  39. Chida Y, Steptoe A. Cortisol awakening response and psychosocial factors: A systematic review and meta-analysis. Biol Psychol. 2009; 80: 265-278.

    Google Scholar 

  40. Melzack R. Pain and the neuromatrix in the brain. J Dent Educ. 2001; 65: 1378-1382.

    PubMed  CAS  Google Scholar 

  41. Blackburn-Munro G. Hypothalamo–pituitary–adrenal axis dysfunction as a contributory factor to chronic pain and depression. Curr Pain Headache Rep. 2004; 8: 116-124.

    Article  PubMed  Google Scholar 

  42. McGue M, Osler M, Christensen K. Causal inference and observational research: The utility of twins. Perspect Psychol Sci. 2010; 5: 546-556.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Kendler KS, Campbell J. Interventionist causal models in psychiatry: Repositioning the mind–body problem. Psychol med. 2009; 39: 881-887.

    Article  PubMed  CAS  Google Scholar 

  44. Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009; 139: 267-284.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  45. Voscopoulos C, Lema M. When does acute pain become chronic? Br J Anaesth. 2010; 105(Suppl 1): i69-i85.

    Article  PubMed  Google Scholar 

  46. De Jongh RF, Vissers KC, Meert TF, et al. The role of interleukin-6 in nociception and pain. Anesth Analg. 2003; 96: 1096-1103. table of contents.

    Article  PubMed  CAS  Google Scholar 

  47. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci. 2005; 6: 521-532.

    Article  PubMed  CAS  Google Scholar 

  48. Malan TP Jr, Porreca F. Lipid mediators regulating pain sensitivity. Prostaglandins Other Lipid Mediat. 2005; 77: 123-130.

    Article  PubMed  CAS  Google Scholar 

  49. Roberts ADL, Wessely S, Chalder T, Papadopoulos A, Cleare AJ. Salivary cortisol response to awakening in chronic fatigue syndrome. Brit J Psychiatr. 2004; 184: 136-141.

    Article  Google Scholar 

Download references

Acknowledgments

This research was supported by National Institutes of Health award R01AR051524 (Dr. Afari). Portions of this research were conducted at the University of Washington Institute of Translational Health Sciences supported by National Institutes of Health awards UL1RR025014, KL2RR025015, and TL1RR025016. Cortisol assays were conducted at the University of Kentucky Center for Clinical and Translational Science supported by the National Institute of Health awards UL1RR033173 and UL1TR000117. Dr. Afari also is supported by the Veterans Administration Center of Excellence for Stress and Mental Health. Dr. Strachan is supported in part by National Institute of Health award R21AI81347. Drs. Afari, Strachan, and Buchwald are supported in part by National Institute of Health award U01DK082325. We wish to thank the twins for taking part in the University of Washington Twin Registry and for their time and enthusiasm for this project. Portions of this study were presented at the 33rd Annual Meeting of the Society of Behavioral Medicine, New Orleans, LA. The content of this research is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Conflict of Interest

The authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA

    Kathryn M. Godfrey MS

  2. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA

    Eric Strachan PhD & Brian Poeschla MD

  3. Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA

    Elizabeth Dansie PhD

  4. Department of Medicine, University of Kentucky, Lexington, KY, USA

    Leslie J. Crofford MD

  5. Departments of Epidemiology and Medicine, University of Washington, Seattle, WA, USA

    Dedra Buchwald MD, Annemarie Succop BA & Carolyn Noonan MS

  6. Department of Epidemiology, Seattle VA Epidemiology Research and Information Center, University of Washington and Vietnam Era Twin Registry, Seattle, WA, USA

    Jack Goldberg PhD

  7. VA Center of Excellence for Stress and Mental Health and Department of Psychiatry, University of California, San Diego, CA, USA

    Niloofar Afari PhD

  8. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, 0737, La Jolla, , CA, 92093, USA

    Niloofar Afari PhD

Authors
  1. Kathryn M. Godfrey MS
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  2. Eric Strachan PhD
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Correspondence to Niloofar Afari PhD.

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Godfrey, K.M., Strachan, E., Dansie, E. et al. Salivary Cortisol and Cold Pain Sensitivity in Female Twins. ann. behav. med. 47, 180–188 (2014). https://doi.org/10.1007/s12160-013-9532-4

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  • DOI: https://doi.org/10.1007/s12160-013-9532-4

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