Stress and Headache Chronification


  • Timothy Houle PhD,

    1. From the Department of Anesthesiology, Wake Forest University Medical School, Winston Salem, NC, USA (T. Houle); The Miriam hospital/Brown University, Providence, RI, USA (J. Nash).
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  • Justin M. Nash PhD

    1. From the Department of Anesthesiology, Wake Forest University Medical School, Winston Salem, NC, USA (T. Houle); The Miriam hospital/Brown University, Providence, RI, USA (J. Nash).
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  • Conflict of Interest: None

Tim Houle, Department of Anesthesiology, Wake Forest University Medical School, Winston Salem, NC 27157, USA.


In this special section, the concept of stress has been linked to the chronification of headache and is considered to be one of several likely mechanisms for the progression of an otherwise episodic disorder to a chronic daily phenomenon. The present review discusses the concept of stress and describes the mechanisms through which stress could influence headache progression. The hypothesized mechanisms include stress serving as a unique trigger for individual attacks, as a nociceptive activator, and as a moderator of other mechanisms. Finally, the techniques used in the screening and management of stress are mentioned in the context of employing strategies for the primary, secondary, or tertiary prevention of headache progression.


Stress and headache are intricately interrelated. Stress is thought to contribute to headache disorder onset in predisposed individuals, trigger or worsen individual headache episodes in those with headache, and exacerbate the progression of a headache disorder. In exacerbating headache disorder progression, stress is believed to be a major factor in headache transformation from an episodic to a chronic condition.1-3

Broadly stated, stress is conceptualized as an imbalance between a demand, whether actual or perceived, and resources to handle the demand, resulting in a strain on the system. A stressor is any challenge or threat, whether objectively verified or not, to normal functioning. The stress response is the body's activation of physiological systems to protect and restore functioning.

Selye4 is most noted for proposing that the physiological response to stress is uniform across individuals and occurs in stages, from initial alarm, to a period of sustained resistance, and ending with exhaustion, as part of a General Adaptation Syndrome. More recently, McEwen5,6 characterized the stress response as an allostatic process. As part of the process, the hypothalamic-pituitary-adrenal axis, involving the interaction of the hypothalamus, the pituitary gland, and the adrenal glands, serves as the system that protects the body in response to stress challenges.7 In response to a stressor, hormones are released including beta-endorphin, a morphine-like hormone that has pain-reducing effects under stress, and cortisol, a steroid hormone that increases heart contractions and sensitizes blood vessels to the effects of norepinephrine. Overexposure to cortisol and other hormones associated with allostatic load can have pathophysiologic consequences.5,6

Richard Lazarus8 is credited with clarifying the factors that account for the individual variation that occurs in stress responses. In his transactional model of stress and coping, Lazarus emphasized the importance of appraisal in determining the stress response. Appraisal determines the magnitude of the stress response and involves the level or threat the stressor poses, the controllability of the stressor, and the perceived ability to cope based on available coping resources.9 The headache specialist Harold Wolff's work in the 1950s was informed by Selye's work and consistent with formulations put forth by Lazarus.10


Although the hypothesis that stress is a risk factor for headache progression has often been postulated,11,12 only very limited direct supporting evidence is available. In a single unpublished examination of this hypothesis using patients from the Frequent Headache Epidemiology Study, cases with new onset chronic daily headache were more likely to have experienced a recent stressful life event (eg, experience a move, a change in relationship, major problem with children) than similar controls who did not have headaches that became more frequent.13 Although the nature of the stress–headache relationship is probably quite variable,14,15 this association is interesting and raises several questions concerning the possible mechanisms through which stress may lead to headache progression.

Even in the absence of direct supporting evidence, there are reasons to believe that chronic stress exposure may be related to headache progression through both direct and indirect mechanisms. Each of these mechanisms is well-grounded in empirical support for specific implications in the onset or maintenance of individual headache attacks. Three of the mechanisms through which stress can affect headache will be briefly explored with special emphasis placed on a possible role in headache progression.

Stress Exposure Influences the Initiation of Acute Headache Attacks.— Stress is the most frequently reported precipitant of headache, with one study finding that >90% of patients endorse that stress affects at least some of their headaches.16 Research examining the stress–headache relationship typically conceptualizes stress as consisting of 1 of 2 categories: daily hassles and major stressful life events. Daily hassles (eg, traffic, deadlines) have been consistently shown to affect daily headache activity.17–19 Individuals with headache report a greater number of daily life hassles than controls.20,21 Headache sufferers, however, do not typically report a greater number of major stressful life events (eg, divorce, illness in family) than controls,16,20 nor do they rate (perceive) experimental stressors differently than controls.20 The nature of the stress–headache relationship is probably quite variable14,15 and still not well understood, but considering that stress exposure facilitates individual attacks, it is logical to postulate that increased stress could lead to increased headache frequency resulting in headache chronification.

Stress Exposure and Nociceptive Activation/Diminished Secondary Modulation.— Acute stress exposure activates an opioid-mediated pain modulation response. This adaptive response serves to temporarily decrease the experience of pain, allowing an individual to better respond to a perceived threat. However, repeated activation of the modulating response in reaction to chronic stress (and distress) can lead to central sensitization, exhausting the central pain control system and leading to hyperalgesia.22,23 Chronic stress (and distress) also sensitizes peripheral nociceptors. Indeed, recent investigations have demonstrated how stress challenges can aggravate pain responses, particularly in those who may have existing central sensitization.24 Following a stress challenge, frequent tension-type headache sufferers with affective distress (ie, depression) showed increased likelihood of tension-type headache and elevated pericranial muscle tenderness compared with those without distress.25 In addition, laboratory stress challenges have resulted in heightened pain elicitation and prolonged pain recovery in headache patients compared with nonheadache controls.26,27 Taken together, the findings from these studies support the notion that chronic stress exposure can lead to central sensitization and that this sensitization increases the likelihood of transformation into chronic daily headache.

Stress Exposure and Its Interrelation With Other Mechanisms.— In addition to its potential for being an independent factor in contributing to headache chronicity, stress also plays an indirect role by influencing a number of the other factors that encourage the progression of headache. For instance, stress associated with fear of pain and the perceived inability to control pain can lead to suboptimal analgesic use, eventually leading to medication overuse and increased likelihood of chronic headache.28,29 Further, stress has complicated and multifarious relationships with sleep,30 eating and the development of obesity,31 and the development and course of psychopathology,32 all of which have been linked with headache progression. Thus, either directly or through indirectly moderating other mechanisms, stress exposure has the potential to influence the course of a headache disorder (or sequelae of the disorder), emphasizing the importance of adequate screening and management.


The assessment of stress can occur in one of several stages that have direct implications for primary, secondary, or tertiary prevention of headache progression.28 Specifically, for individuals who are predisposed to having a headache disorder (eg, strong family history, initiation of some attacks), the monitoring of stress (ie, daily hassles, stressful life events) may lead to an increased awareness of the concept and the development of specific coping skills that can minimize the risk of the expression of the headache disorder.28 For individuals who are already experiencing episodic attacks, developing an awareness of the specific impact that stress has on individual attacks, perhaps as a triggering or exacerbating influence, may result in an increased sense of control over the headaches, improving adjustment.28,33 Finally, for individuals who have already experienced the progression of their headache disorder, monitoring the interplay of stress with other risk factors (ie, medication use and sleep) could be part of a comprehensive strategy for a potent intervention.

There are several methods that can be used to assess (“screen”) stress that could be employed for a wide range of therapeutic goals. First, a clinical interview could be used to assess a patient's perception of the challenges, threats, and barriers that currently confront them. Further, a daily stress diary could be employed, either using a validated (see the study by Brantley et al34) or less structured instrument, to track the experience of stress over some observation period. Finally, the patient's significant other and/or extended family members could also be interviewed to examine the contextual nature of the stress experience. The practical limitations of the setting will often dictate the extent of the assessment process, but a good assessment of a patient's perceived resources for dealing with stressors will enhance the selection of an appropriate treatment strategy.

There are many treatment strategies that involve stress reduction that have empirical support in the management of primary headache.10,35,36,37 These strategies are effective at reducing both headache activity and headache-related disability. Cognitive-behavioral therapy is a popular treatment that includes specific stress management components along with some form of physiological self-regulation (eg, relaxation or biofeedback training).3–7 Stress management training for headache provides individuals more adaptive ways of interpreting (ie, cognitive restructuring) and managing stress through the application of coping skills. Taken together, these interventions target both the perception and the management of stressors and can be applied in a diverse group of settings for any number of specific treatment goals. These behavioral strategies are quite effective for improving stress management and are likely to be similarly effective in the prevention/treatment of headache progression.