Elsevier

Psychoneuroendocrinology

Volume 71, September 2016, Pages 127-135
Psychoneuroendocrinology

Invited review
Dysfunctional stress responses in chronic pain

https://doi.org/10.1016/j.psyneuen.2016.05.017Get rights and content

Highlights

  • Many dysfunctional and chronic pain conditions overlap.

  • Chronic deregulation of the adaptive response to stress may be the common factor.

  • The HPA axis, neuro-steroids, autonomous nervous and immune systems are implicated.

  • Individual vulnerability to stress can be due to environmental and genetic factors.

Abstract

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints.

Section snippets

Introduction: dysfunctional pain

Many chronic conditions, with or without pain, are qualified by the terms “functional”, “non-specific” or more appropriately “dysfunctional”. Among the best known dysfunctional pain conditions are fibromyalgia, some low back pain syndromes, temporo-mandibular disorders, tension-type headache, irritable bowel syndrome, complex regional pain syndrome, atypical facial pain, burning mouth syndrome, and vulvodynia. Although many were identified recently as separate conditions, they have much in

The adaptive responses to stimuli

Since its introduction in the 1930s by Selye (1950), the term “stress” has become a commonplace concept whose meaning remains vague (Heuser and Lammer, 2003). There are three commonly meanings of the term. The stimulus proper or “stressor”, real or perceived, arises from common life events such as social interactions requiring mental, emotional or physical activity; they modify the homeostasis equilibrium directly or potentially by anticipating what may happen (Selye, 1950, McEwen, 2000). In

Conclusions

Large differences exist in the type of deregulation of the physiological response to stress and lead to pathophysiological differences between pain conditions. There is also much heterogeneity in the dysfunctions of the HPA-ANS systems observed in patients belonging to the same pain groups. These differences and heterogeneities may in part explain the differences in the clinical pictures (Clauw and Ablin., 2009). Complex interactions also occur in chronic pain conditions not only between the

Contributions

Pr Woda designed the review. Pr Woda and Dr Dutheil drafted the manuscript. Dr Picard revised the manuscript. All authors revised and approved the final version submitted for publication.

Funding

None.

Acknowledgement

We are thankful to Mr Jeffrey Watts for his English proof editing.

References (133)

  • H. Cohen et al.

    Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability

    Semin. Arthritis Rheum.

    (2000)
  • L.J. Crofford

    The hypothalamic-pituitary-adrenal axis in the pathogenesis of rheumatic diseases

    Endocrinol. Metab. Clin. North Am.

    (2002)
  • L. Diatchenko et al.

    Idiopathic pain disorders—pathways of vulnerability

    Pain

    (2006)
  • B.O. Dubrovsky

    Steroids, neuroactive steroids and neurosteroids in psychopathology

    Prog. Neuropsychopharmacol. Bol. Psychiatry

    (2005)
  • M.J. Essex et al.

    Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior

    Biol. Psychiatry

    (2002)
  • E. Fries et al.

    A new view on hypocortisolism

    Psychoneuroendocrinology

    (2005)
  • J. Gaab et al.

    Reduced reactivity and enhanced negative feedback sensitivity of the hypothalamus-pituitary-adrenal axis in chronic whiplash-associated disorder

    Pain

    (2005)
  • U. Galli et al.

    Enhanced negative feedback sensitivity of the hypothalamus-pituitary-adrenal axis in chronic myogenous facial pain

    Eur. J. Pain (London, England)

    (2009)
  • A. Geiss et al.

    Evidence for an association between an enhanced reactivity of interleukin-6 levels and reduced glucocorticoid sensitivity in patients with fibromyalgia

    Psychoneuroendocrinology

    (2012)
  • P.R. Geissler

    An investigation of the stress factor in the mandibular dysfunction syndrome

    J. Dent.

    (1985)
  • A.M. Hansen et al.

    Frequency of bullying at work, physiological response, and mental health

    J. Psychosom. Res.

    (2011)
  • A.R. Hariri et al.

    Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing

    Biol. Psychiatry

    (2006)
  • I. Heuser et al.

    Stress and the brain

    Neurobiol. Aging

    (2003)
  • B.J. Jogems-Kosterman et al.

    Basal cortisol and DHEA levels in women with borderline personality disorder

    J. Psychiatr. Res.

    (2007)
  • D.A. Jones et al.

    The cortisol response to psychological stress in temporomandibular dysfunction

    Pain

    (1997)
  • E.D. Kanter et al.

    Glucocorticoid feedback sensitivity and adrenocortical responsiveness in posttraumatic stress disorder

    Biol. Psychiatry

    (2001)
  • B.M. Kudielka et al.

    Cortisol day profiles in victims of mobbing (bullying at the work place): preliminary results of a first psychobiological field study

    J. Psychosom. Res.

    (2004)
  • P.A. Lapchak et al.

    Preclinical development of neurosteroids as neuroprotective agents for the treatment of neurodegenerative diseases

    Int. Rev. Neurobiol.

    (2001)
  • A.M. Mankus et al.

    Mindfulness and heart rate variability in individuals with high and low generalized anxiety symptoms

    Behav. Res. Ther.

    (2013)
  • J. Marsac

    [Heart rate variability: a cardiometabolic risk marker with public health implications]

    Bull. Acad. Natl. Med.

    (2013)
  • B.S. McEwen

    The neurobiology of stress: from serendipity to clinical relevance

    Brain Res.

    (2000)
  • B.S. McEwen

    Glucocorticoids, depression, and mood disorders: structural remodeling in the brain

    Metabolism

    (2005)
  • M. Meeus et al.

    Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review

    Semin. Arthritis Rheum.

    (2013)
  • R.C. Melcangi et al.

    Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves

    Prog. Neurobiol.

    (2003)
  • R.C. Melcangi et al.

    Peripheral nerves: a target for the action of neuroactive steroids

    Brain Res. Brain Res. Rev.

    (2005)
  • H. Montgomery et al.

    Angiotensin-converting-enzyme gene insertion/deletion polymorphism and response to physical training

    Lancet

    (1999)
  • K.B. Nilsen et al.

    Autonomic activation and pain in response to low-grade mental stress in fibromyalgia and shoulder/neck pain patients

    Eur. J. Pain (London, England)

    (2007)
  • T. Rinne et al.

    Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

    Biol. Psychiatry

    (2002)
  • M. Ritsner et al.

    Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients

    Eur. Neuropsychopharmacol.

    (2004)
  • R. Riva et al.

    Comparison of the cortisol awakening response in women with shoulder and neck pain and women with fibromyalgia

    Psychoneuroendocrinology

    (2012)
  • R. Rupprecht

    Neuroactive steroids: mechanisms of action and neuropsychopharmacological properties

    Psychoneuroendocrinology

    (2003)
  • A.N. Salicru et al.

    Cooperative effects of corticosteroids and catecholamines upon immune deviation of the type-1/type-2 cytokine balance in favor of type-2 expression in human peripheral blood mononuclear cells

    Brain Behav. Immun.

    (2007)
  • I. Sayeed et al.

    Allopregnanolone, a progesterone metabolite, is more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion

    Ann. Emerg. Med.

    (2006)
  • M. Schumacher et al.

    Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

    Prog. Neurobiol.

    (2003)
  • R. Sesti-Costa et al.

    Chronic cold stress in mice induces a regulatory phenotype in macrophages: correlation with increased 11beta-hydroxysteroid dehydrogenase expression

    Brain Behav. Immun.

    (2012)
  • J.N. Ablin et al.

    Biomarkers in fibromyalgia

    Curr. Pain Headache Rep.

    (2009)
  • J. Achten et al.

    Heart rate monitoring: applications and limitations

    Sports Med.

    (2003)
  • E.K. Adam et al.

    Day-to-day dynamics of experience–cortisol associations in a population-based sample of older adults

    Proc. Natl. Acad. Sci. U. S. A.

    (2006)
  • M. Baumert et al.

    Heart rate variability, blood pressure variability, and baroreflex sensitivity in overtrained athletes

    Clin. J. Sport Med.

    (2006)
  • D. Belelli et al.

    Neurosteroids: endogenous regulators of the GABA(A) receptor

    Nat. Rev. Neurosci.

    (2005)
  • Cited by (0)

    View full text