Pain cognition in migraine: from basic neurophysiology to a behavioral paradigm

DOI: https://doi.org/10.1007/s10072-018-3335-0

Abstract-Summary Most of the data in this review have been already reported by the authors in Neurological Science, but the goal of the present paper is to realize an integrated lecture of all the available data and look to the last achievements in pain cognition, with a special focus on migraine and chronic migraine.

The Evolving Concept of Pain As argued by Craig: “the human feeling of pain is both a distinct sensation and a motivation that is a specific emotion that reflects homeostatic behavioral drive, sim- ilar to temperature, itch, hunger, and thirst” [558].

Pain is regarded as a modality to restore homeostasis, including anticipatory behavioral measures to prevent whatever impending derangement of the homeo- static balance [559].

This new conception of pain makes it closer to other sensory modalities in which the perception of a stimulus, more or less complex, induces at the same time an emotion, a motivation, and an adaptive behavior.

This process requires the interplay of brain areas involved at least in somatic sensation, in emotion modulation, in memory and cognitive processing, and in veg- etative control and motor behavior, and must include inhibitory/facilitatory mecha- nism for the control of ascending painful signals.

Migraine as an Inescapable Visceral Pain The conceptualization of pain as a powerful homeostatic emotion enables its inter- pretation in terms of biobehavioral response according to different stimuli and espe- cially to the context in which pain is generated.

4.8 Psycho-Behavioral Interventions

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In this key, migraine has to be conceptualized as an inescapable pain, i.e., the pain that indicates a problem that cannot be successfully faced up, or that would be even counterproductive trying to control by any active defensive behavior.

Inescapable pain pathways to the brain involve the PAG, especially its ventrolat- eral part [560] with projections to the hypothalamus, amygdala, and forebrain [561, 562].

It is noteworthy that, at least for visceral homeostatic pain, the neural network involved in its processing almost completely overlaps with the so-called pain matrix [563], the network of brain areas activated by pain arising from different sources and considered implied in the development of allodynia and of some of its related primary pain disorders such as fibromyalgia and neuropathic pain.

From the Pain Matrix to the Neurolimbic System On the basis of several neurophysiological studies, the migrainous brain is charac- terized by the lack of cortical habituation phenomenon for both non-painful and painful repetitive stimuli in the interictal phase; on the contrary, during the attack phase, the habituation phenomenon normalizes for non-painful stimuli, while an impaired habituation for repetitive painful stimuli is observed up to a central sensi- tization [564].

The availability of functional brain studies has led to new insight in migraine pathophysiology and to the definition of brain structures and above all of the net- works involved in different migraine phases.

The intriguing study by Schulte and May [565], exploring an entire migraine cycle by performing in migraine patients a daily fMRI for 30 days consecutive and “recording” three migraine attacks, has demonstrated the alteration of the functional connection between hypothalamus and trigeminal nuclei and dorsal pons, revealing more than the existence of a “migraine generator,” the existence of an oscillation in the functional connectivity between the several structures involved in “migraine experience.”

Migraine Trigger Factors and the Lymbic System An intriguing unitary hypothesis that could explain how such multiple and different triggers may be involved in migraine pathophysiology, preserving at the same time the relevance of peripheral trigeminal input, has been proposed by Burstein and Jakubowski [566].

These authors observed that many different known migrainous triggers are pro- cessed in several hypothalamic nuclei and other limbic areas, all connected to the superior salivatory nucleus (SSN).

Since the ascending trigeminal pathways accounting for the accompanying symptoms of the migraine attack project to the same specific limbic areas (hypo- thalamus, midbrain, amygdala, basal forebrain) whose converging output on SSN had triggered the trigeminal vascular activation itself, a possible positive feedback loop of this articulated circuitry could account not only for the triggering but also for the perpetuation of a migraine attack for hours or days.

What Happens When Migraine Shifts to Chronicity? Allodynia has been included among the risk factors for migraine progres- sion [567].

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4 Treatment

If allodynia promotes the progression of migraine pain, individual susceptibility

to pain sensitization may play a crucial role in CM development.

Analgesic overuse, elevated frequency at baseline, psychiatric comorbidity, obe- sity, and female gender are the main validated factors associated with the progres- sion of migraine pain.

A comorbidity with an overlooked idiopathic intracranial hypertension (IIH) without papilledema (IIHWOP) has been recently proposed as a relevant risk factor for migraine progression and refractoriness [568].

In a recent survey [569], depression was independently associated with high scores on the cutaneous allodynia scales, suggesting again that a central sensitiza- tion could represent the shared pathogenetic mechanism underlying migraine and the comorbidity of psychiatric disorders.

A Behavioral, Integrated Migraine Perspective In this very interesting reconceptualization of primary headaches, the inextricable puzzle represented by the multifaceted clinical characteristics of the migraine pain attack can be solved considering its striking similarity with the innate, pan-mamma- lian, adaptive behavioral response to visceral “inescapable” pain represented by what Hart termed sickness behavior [570].

In this light, the clinical complexity of the migraine attack presentation could reflect the “physiologic” allostatic response to internal or external stimuli perceived (more or less inappropriately in migraineurs) as a body homeostasis threat to pro- mote the homeostatic imbalance restoration through a temporary retire of the indi- vidual from any environmental interaction, including that arising from ordinary daily life activities.

In the Montagna et al. finalistic adaptive view of migraine, the stereotyped but enigmatic array of symptoms, signs, emotions, and behaviors that characterize the migraine attack could rely on an ancient, evolutionary modeled, anatomical network that aimed to promote the mammalians sickness behavior in response to brain, or whole organism, homeostatic balance threat.

Acknowledgement A machine generated summary based on the work of Bonavita, Vincenzo; De Simone, Roberto; Ranieri, Angelo. 2018 in Neurological Sciences.

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