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Clinical and Translational Neuroscience
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  • Essay
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9 December 2025

The Uprising of an Exhausted Brain—An Imperativist View of Migraine

Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland
Clin. Transl. Neurosci.2025, 9(4), 57;https://doi.org/10.3390/ctn9040057
This article belongs to the Section Headache
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Abstract

Considering the prevalence of migraine and its impact on everyday living, its evolutionary persistence remains puzzling. This essay reviews recent literature and conceptual perspectives that frame migraine attacks as a possible side-effect of prolonged stress and unmet needs. To illustrate this, the article compares the antithetical relationship of triggers and migraine symptoms: During the early phase of the attack, many eat, drink, rest and sleep more and tolerate less nuisance compared to the hours and days before; previously, however, there was too little time to eat, drink, rest, and sleep, and the nuisance had to be tolerated. A relevant characteristic of many migraineurs is that they are prone to stress, e.g., because of a character trait, an impaired adaptation to stress, the lack of habituation to sensory stimuli, and disturbances of the energy supply. In that way, the appearance of the attack during fading stress makes sense: the body seizes the opportunity and communicates its needs when circumstances permit. In this context, the concept of pain as an imperative—a signal designed to enforce behavioural change—provides an insightful framework. Understanding migraine in this way may help reframe its pathophysiology and its clinical and translational significance.

1. Introduction

Affecting one in eight people each year [1] and one in three during their lifetime [2], a remarkable property of migraine is its prevalence. It is so common that some wonder if there is a benefit to it. After all, would not evolution have eradicated migraine if it were pure dysfunction [3,4,5]? On the other hand, evolution has not resolved many of the inconveniences of the human condition. Perpetual well-being is not one of its prime achievements.
Many migraineurs report that their attacks occur as stress subsides [6], and some even welcome the “me-time” they bring [7], suggesting some connection with exhaustion or insufficient rest. So, it is tempting to speculate that prolonged stress overstrains the nervous system, thus paving the way for the attack. Observing nature supports this idea: many species can temporarily ignore their basic needs and exhaust themselves when circumstances require it, even at the risk of disastrous consequences [8].
Salmon swimming upstream to spawn, facing death upon arrival, demonstrate the extremes reached when exhaustion is ignored [8,9]. The advantage of being able to surpass what was believed to be the limit of the physically possible is that the increased availability of energy resources in times of danger and adversity can facilitate survival [10].
Exhaustion has many causes; physical activity is just one of them, and it is not the most potent trigger of an attack. Regardless of its cause, exhaustion makes repose imperative, and pain acts as a powerful mechanism to enforce this halt. Appropriately, migraine attacks also enforce a halt. However, the intricate symptoms of the attacks do not comprise pain alone, and their behavioural effects go far beyond ordering rest.
Starting with pain—the most obvious attack symptom—this article discusses how behavioural changes are intrinsic to migraine and contrast its triggers. Finally, it argues that the concerted action of the brain during attacks does not imply dysfunction; instead, it suggests that ignoring the body’s needs and failing to accommodate adversity may predispose to an attack.
Please note that the perspectives presented in this article are intended to stimulate discussion and reflection. While grounded in scientific knowledge, some of the views expressed are speculative.

2. Imperatives—Stewards to the Nonconscious Mind

When asked about the purpose of pain, one might intuitively assume that it informs about tissue distension or damage. However, only nociceptive pain arises from a threat to the body’s integrity; the other two currently distinguished types—neuropathic and nociplastic pain—do not [11]. Neuropathic pain results from damage to nerve cells; nociplastic pain is neither neuropathic nor nociceptive, and its cause is largely unknown [12]. In addition, even nociceptive input does not invariably result in pain [13], and when it does, it conveys very little information.
The spatial information transmitted by nociceptive pain is imprecise—sometimes, it occurs at a distance from its source [14,15,16]. In addition, nociceptors that screen the tissue for damage transmit their signals slowly, compared with sensory neurons [17]—if they aim to communicate something, they are certainly not in a hurry. In addition, even for seasoned neurologists and emergency physicians, let alone for affected persons themselves, distinguishing the three types of pain can be difficult at times [18].
So, perhaps, the purpose of pain is not primarily to inform but to influence behaviour; intense pain’s capability to modify behaviour is evident irrespective of its type. For instance, pain that feels like it is caused by inflammation urges us to rest; pain that feels like it is due to an external source triggers restlessness [19].
The behaviour change is certainly not without cause. Resting as a response to pain stemming from within the body presumably allows for recovery by conserving energy. Conversely, the restlessness in response to pain stemming from an external source most likely predisposes to fleeing and fighting, thereby increasing survival chances [19].
Since the urge to adapt one’s behaviour when in pain can be very strong, some authors view pain primarily as an “imperative” issued by the brain; appropriately, their school of thought is called “imperativism” [20]. Consequently, pain could mainly constitute a call of the nonconscious mind to behave differently.
Imperatives represent behavioural messages from the human brain that prompt changes in behaviour. Examples are thirst, hunger, and tiredness. They all aim to keep the body operable. They can be ignored for some time when circumstances require, especially when more significant threats to maintaining a functioning state arise. However, the underlying need for food, drink, and sleep remains even when responding to these imperatives is delayed.
Broadening the sense of the word, there is a different class of imperatives that primarily regard our interaction with the outside world and aim to mitigate adversity. Sigmund Freud has written extensively about humans’ drives to avoid aversion, each in their own means and according to their standards, many of which were set during early childhood [21].
Therefore, the nonconscious mind influences and stewards the human will through imperatives. Very little is known about most of the mechanisms used to achieve that goal, except for pain, which has been extensively studied.

3. The Physiology of Pain-Related Behavioural Changes

Nociceptive pain results from nociceptive input signalled to the brain through nociceptors. Spread throughout the tissue, they monitor for distension and damage resulting from pressure, inflammation, heat, and cold. There are two types of them: A delta nociceptors and C nociceptors [22]. The former respond to sharp damage, and the latter to poorly localised input, as in inflammation [23,24].
Their signals reach the spinal cord, where so-called descending pathways, known for their role in the placebo effect, can attenuate them [25,26]. Once their input arrives in the brain, it is relayed from the thalamus to other brain areas, including the anterior cingulate gyrus and the posterior insula [27].
Studies showed that the different types of pain (C fibre- and A delta fibre-mediated pain) activate the anterior cingulate gyrus differently, possibly leading to different activation patterns of the periaqueductal grey located in the brain stem [28]. Subsequent animal studies showed that the activation of the periaqueductal grey is associated with specific behaviours, either restlessness or quiescence [29,30]. Their significance for survival is evident: when under attack, it makes sense to prepare for fighting; when disease rages within, resting and conserving energy reserves for the immune system may allow for survival [19].
Magnetic resonance imaging studies of humans during a migraine attack also indicate an activation of the periaqueductal grey [31]. Since migraineurs liken the headache to C fibre-mediated pain and tend to lie down during their attacks—as is also observed in C fibre-mediated pain—it is plausible that the brain’s activation pattern during migraine pain closely resembles that seen in C fibre-mediated pain.
Accordingly, withdrawing to a bedroom during a migraine attack is common [32], but unlikely to be a conscious and considered response to pain. Instead, the drive to do so is involuntary and mediated by a pain that feels as if it stems from within the body.
It can hardly be a coincidence that most people lie in their beds, which, on countless nights before, have proven to lend themselves to energy saving and restoration [33]. It is tempting to speculate that having a bedroom—a private haven—may be an innate human need. After all, a bed may be considered the part of the outer world entrusted most with serving the body’s needs for repose—a foothold of the inner world, as it were.
The permanent availability of a bedroom within a house—protecting from many external dangers—is an attainment resulting from society’s shift from a nomadic to a sedentary lifestyle. Valença et al. suggest that the behavioural consequences of migraine—particularly the periodic need for a safe place to rest—may have even favoured such adaptations in early human societies: as communities grew larger, the number of individuals incapacitated by migraine attacks at any given time likely increased; as a result, constant roaming became more difficult, while the need for a space to withdraw increased simultaneously [34].
Overall, migraine attacks force a rest upon the affected as if there were an internal disease or an infection. It would be a strange coincidence if the same pathways were used purposefully in nociceptive pain and in the same way, but by accident or dysfunction in migraine.
Interestingly, there are many additional imperatives at play in migraine.

4. Migraine Attacks—A State of Blaring Imperatives

Migraine is a pain disorder characterised by recurring painful spells, each lasting several hours to a few days. Although pain is a hallmark of the attacks and certainly often the most bothersome symptom, it is not the only manifestation of the disorder [35]. While the intensity, quality, and location of pain can differ starkly between individuals [36], the accompanying symptoms validate the diagnosis [37]. A “textbook migraine attack” is often described as having three phases (four, if you count the aura, which is not the topic of this article), with the second phase typically being the most painful [38].
Oftentimes, migraine attacks announce themselves hours before the pain. During this premonitory phase, the affected may experience non-painful symptoms (see Table 1). There is some idiosyncrasy to this part, with symptoms differing individually. Nevertheless, many of them indicate altered behaviour in areas governed by drives largely inaccessible to will, the imperatives above-mentioned.
Table 1. Selection of non-painful symptoms of a migraine attack and their corresponding triggers [39,40,41,42,43,44].
Many people drink more, eat more, experience increased fatigue, and urinate more frequently [39]. In addition, many struggle to concentrate, and thus suspend their intellectual work to rest, if circumstances permit; some feel tension in their neck muscles that hints at the pain to come that will enforce the pause [39].
The first and second phases transition seamlessly, as pain levels rise. The headache can be one-sided (66.6%), focused on the forehead (55.9%), spread to the whole head (17.5%), or radiate to the neck (39.7%) [36]; it may pulsate, especially when moving, so moving is avoided [36,45].
The pain is dull and poorly localised without clear borders and is thus experienced as stemming from the inside of the body, rather than sharp, demarcated pain, which would feel like being inflicted from the outside [46]. It stands to reason that the quality of migraine pain is the root of the impulse to retreat to a quiet space, often a bedroom if circumstances allow, and lie down, which is very prevalent and usually difficult to resist [19].
At the latest during this second phase (see Table 1), many find sound and light displeasing and strongly prefer silence and darkness; loss of appetite, nausea, and vomiting are prevalent [39]. The latter does not constitute a behavioural change in the strict sense. However, it does suggest that the intestine has become very weary of discomfort and hence has a low threshold for voiding. Such intolerance may be the main feature of migraine attacks: Every influence of the outer world is felt more intensely and avoided more eagerly than in the hours and days before the attack (see below).
With pain abating, the third phase, known as the postdrome (see Table 1), begins, during which symptoms, most commonly fatigue and asthenia, gradually resolve [43].
Suppose that imperatives increase in conspicuity during the attacks as described above and do not do so by chance but in response to the circumstances. In that case, we must ask which circumstances could lead to them. The time leading up to the attack may provide the answer.

5. Triggers—The Impetus of Migraine Attacks

A majority of migraineurs consider their migraine attacks not to occur randomly but in response to specific, non-painful triggers they were exposed to in the hours and days before the attack [40]. Thus, we must assume that a “trigger phase” precedes the premonitory phase.
The behaviour experienced during the attack bears some stark resemblance to some of what many recall as triggers of their migraine attacks [41]; many attack symptoms have corresponding triggers that are antithetical (see Table 1). Instead of resting, drinking, and eating more, they rest, drink, and eat less. Instead of withdrawing to a dark, calm room, they are exposed to bright lights and loud noises. Thus, a counterresponse suggests itself: to make up for the time before the attack, the body now appears to demand time to rest and recover, and therefore responds very sensitively to every adversity.
While it may seem simple—ignoring the body’s needs leads to a rebound, namely an increased conspicuity of imperatives—it is not. Studies have exposed migraineurs to their triggers, e.g., intense light and strenuous exercise, and only a few of them had a migraine attack afterwards [47]. Thus, although surveys do suggest a relationship between triggers and pain [40,41,42], it appears weak and somewhat tenuous. Instead, neglecting one’s needs could be an epiphenomenon; the same factors that precluded responding to needs and avoiding adversity also paved the way to the migraine attack.
The best predictive value for the advent of an attack is the cessation of stress, not stress itself [6]. The shift from stress to relaxation implies transitioning from being unable to cope with one’s discomforts to a state that finally allows for addressing them. It makes sense for the body to seize the opportunity and communicate its needs when circumstances permit.
Unfortunately, “stress” is often poorly defined, and studies that collect self-reported triggers do not clarify what the respondents meant [40,41,42].
Analysing some commonly cited triggers (see Table 2) suggests that the stress that migraine patients refer to seems to stem from having abided in an unpleasant situation without focusing attention away from the outer world. They fall into one of four categories depending on whether they comprise (i) unpleasant stimuli from the outer world, (ii) the forced and prolonged concentration on the outer world in times of stress, (iii) the increased strenuousness of focusing on the outer world in times of physical malaise, and (iv) the neglect of the body’s physical needs (see Table 2).
Table 2. Overview of triggers associated with migraine attacks.
Alcohol consumption, particularly red wine, is a frequently mentioned albeit relatively weak trigger [48] that does not fit into any category (see Table 2). Seen through the conceptual framework laid out in this article, drinking alcohol is rather an indicator of abating stress than a trigger; the role of fading stress will be discussed in further detail below.
The relationship between the symptoms of the premonitory phase and their corresponding triggers (see Table 1) suggests a rebound effect whose main driving force is stress. Supporting the idea, there is evidence stemming from therapeutic interventions that stress plays a role in the occurrence of migraine attacks.
For instance, not allowing stress levels to remain high for too long obviates attacks: sports and relaxation techniques—activities that temporarily decrease stress levels—have proven effective at reducing the likelihood of migraine attacks [49,50,51,52]. Likewise, pharmacological preventatives, such as beta-blockers [53], which reduce stress [54], and amitriptyline, which may improve sleep quality [55], can reduce the number of migraine days.
However, migraineurs are not the only ones experiencing stress; so are others [56]. What is the difference between them?

6. Changes in the Conspicuity of Imperatives

The organisation of life in Western societies allows for studying the changing conspicuousness of imperatives: many change their lifestyle as the workweek draws to a close, job-related pressure abates, and mood improves [57]. On the weekend, many people sleep longer [58], eat more [59,60,61] (including sweets and chocolate [62]), gain more weight [63], drink more, and pass urine more frequently [64]; besides, their average blood pressure tends to decrease [65].
While one reason for the behavioural changes on the weekend may be the freedom to decide how to spend the time, it is probable that many also respond more readily to signals from the body. Thus, in some ways, many people’s Saturdays resemble a premonitory phase of a migraine attack. Non-migraineurs may also have been unable to respond to their body’s imperatives during the past workweek.
Appropriately, migraineurs face the highest probability of an attack on Saturdays [66]. However, non-orthopaedic pain does not generally seem to occur more often on that day; at least, opioid analgesics are prescribed equally or even less frequently [67,68,69]. Thus, not all types of pain are likely to be felt more intensely or to occur more frequently on the weekend, suggesting that migraine and its function to order a halt are independent from other types of pain.
Following the above-mentioned idea of a rebound, psychology could explain why migraineurs often do not just enjoy life on the weekend but have migraine attacks instead. Of the many character traits attributed to people with migraine, only neuroticism, defined as the tendency to experience intense negative emotions in response to stress [70], has stood the test of time [71].
Consequently, migraineurs are more likely to be stuck in an unpleasant situation. Still, they must focus all their attention and energy on one task, thus ignoring the imperatives of low conspicuity. Their rebound may often be more intense than that of the average person. Luckily, stress [72] and, to some degree, perhaps even neuroticism [73] decrease with increasing age, just as migraine frequency does [74].
Research on what triggers stress in migraineurs compared to controls could provide further insight, especially given that there are significant differences in what a person perceives as stress.
The adaptation to stressful situations is called allostasis; its mechanisms include the autonomic nervous system, the hypothalamic–pituitary–adrenal axis, metabolic systems (including the thyroid axis, insulin/glucagon production, and the gut), and the immune system [75]. When adaptive mechanisms are over- or underactive, i.e., in maladaptive stress responses, the result is known as allostatic load, i.e., the “wear and tear” on the body and mind. It may manifest as, e.g., impaired hippocampal function, blood pressure increases, vulnerability to infections and possibly cancer, abdominal obesity—and migraine attacks [8,76]. Borsook et al. suggested that allostatic load could negatively impact the functioning of brain networks, which increases the likelihood of migraine attacks, which themselves could constitute allostatic load, potentially increasing the possibility of further attacks [8].
Interestingly, there is some evidence suggesting an impaired adaptation to stress in migraineurs. For example, autonomic nervous system testing has often shown reduced sympathetic signalling in persons with migraine, though findings vary between studies [77,78]. In addition, specific immune phenotypes could increase the risk of migraine [79]; these findings fit nicely in the growing body of evidence suggesting an implication of the immune system in the occurrence of migraine attacks [80,81].
While in some persons with migraine the adaptation to stressors could be impaired, others could be presented with an overwhelming number of stressors or triggers.
A further factor that could predispose to stress in response to sensory stimuli is the difficulty in habituating. Electrophysiologic studies, such as visual and auditory evoked potentials, have shown that the amplitude of the cortical response to stimuli like bright lights and sound does not decrease with repeated exposure in migraineurs, unlike in many people without migraine [82,83]. It is therefore thinkable that these individuals are more likely to feel distracted, disturbed, and ultimately unwell when exposed to such stimuli and require recovery afterwards.
Additionally, there is evidence suggesting metabolic disturbances in some migraineurs, possibly implying that energy demand occasionally exceeds the available energy [84,85]. These could give rise to a different type of overstraining, which would require recovery afterwards.
Rebound or contrast phenomena are well known in humans and animals. They gained broader attention through the works of Solomon, who described “opponent processes” [86]. He reported that a negative reinforcer, i.e., removal of an unpleasant stimulus present before (state A), could lead to a period characterised by the relative absence of emotions, which then resolves into a state of positive emotions (state B). He coined the term “negative contrast” for this phenomenon.
In migraine, it is easy to see how prolonged stress could have led to negative emotions and its cessation to an emotional contrast. Indeed, some patients report feeling in a good mood towards the end of their attacks; however, this is probably not the case for most of them [39,43,87]. Instead, many report similar emotions at the beginning and end of the attack [88].
Unfortunately, most studies have asked only for “mood changes” in the postdrome, without providing further information on their nature [88,89]. Nevertheless, affective contrast and a reaction to fading stress may have different mechanisms, but both are unlikely to constitute a defect.
The time course of the symptoms of a migraine attack is similar in most patients [87]. Thus, the changes in imperatives occur in an orderly manner, making pure dysfunction seem less probable. After all, migraine attacks may indeed be “just” an exaggerated reaction to the stress and adversity of the past days.
So, assuming that migraine is not pure dysfunction, is it helpful to bear a migraine attack without treating it? So far, the available evidence provides no reason to believe that renouncing pharmacological intervention such as triptans or neuromodulatory devices is beneficial. The reason is that acute medication is usually taken only during the premonitory phase of an attack, when most of the imperatives have already exerted their influence. After all, these premonitory symptoms allow for the detection of the incipient attack. In addition, several drugs result in tiredness themselves and thus preclude returning to a stressful life immediately [90].
Therefore, current acute treatment options may not allow for the study of potential side effects of not bearing the attacks until their end. Conversely, there have been speculations about migraine attacks being stressful themselves and also resulting in a higher migraine frequency [8]. Consequently, much remains to be studied about the role and the relevance of rebounding imperatives.

7. Critical Reflection/Limitations

This article is presented in the form of an essay. As such, it does not aim to provide new empirical data or statistical analysis, but rather to synthesise existing literature and explore conceptual perspectives. The intended purpose of the speculative elements is to stimulate discussion and reflection, not to offer a definitive conclusion.
Considering imperatives and their conspicuity may help understand the dynamics of migraine attacks. Patients’ concordant self-reported observations, published in numerous articles over the years, inspired this paper. However, although the attacks appear generally similar, not everyone experiences them the same way or reports triggers [40]. Migraine with aura stands out most evidently, as it occurs more frequently without identifiable triggers [40].
While pain may certainly outshine less evident symptoms, and detecting triggers may require having lived through many attacks, it may also be true that some people do not have triggers.
Lastly, not every premonitory symptom has a corresponding trigger. In addition, it is challenging to differentiate triggers from premonitory symptoms; the choice made in this article supported its main idea, but could have been made differently.
While it seems likely that pain has the purpose of imposing a halt on patients who have been unable to obey their imperatives, this may not be the reason for the attacks in everyone. Further research, perhaps with an updated or revised conceptualisation, is required for them.

8. Conclusions

During the early phase of a migraine attack, many people eat, drink, rest, and sleep more, and tolerate less nuisance compared to the hours and days leading up to it. Previously, they endured adversity without adequately addressing their own needs. There was too little time to drink, eat, rest, and sleep, and the nuisance had to be tolerated. Migraine, in response, imposed a complete stop in an orderly manner and similarly among different persons. A counterresponse enforces a temporary withdrawal through pain and behavioural changes, hardly accessible to one’s own will. A dysfunction seems unlikely given the concerted action; genetics might only predispose for stress of different origins, but not necessarily the pain itself, which is optional. After all, migraine attacks could well be just an uprising of an exhausted brain.

Funding

The author was funded by Werner Dessauer Stiftung.

Institutional Review Board Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The author declares no conflicts of interest.

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Promoting Brain Health: Report on Activities of the Bern Brain Health Working Group
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