The Lack of Peripheral Pathology in Migraine Headache

Abstract

This article reviews the baffling problem of the pathophysiology behind a peripheral genesis of migraine pain--or more particularly the baffling problem of its absence. I examine a number of pathophysiological states and the effector mechanisms for these states and find most of them very plausible and that they are all supported by abundant evidence. However, this evidence is mostly indirect; to date the occurrence of any of the presumed pathological states has not been convincingly demonstrated. Furthermore, there is little evidence of increased trigeminal sensory traffic into the central nervous system during a migraine attack. The article also examines a number of observations and experimental programs used to bolster a theory of peripheral pathology and suggests reasons why they may in fact not bolster it. I suggest that a pathology, if one exists, may be in the brain and even that it may not be a pathology at all. Migraine headache might just happen because of random noise in an exquisitely sensitive and complex network. The article suggests an experimental program to resolve these issues.

Cortical spreading depression and central pain networks in trigeminal nuclei modulation: time for an integrated migraine pathogenesis perspective

“…This study provides the basis for a possible direct central top-down triggering of the migraine pain, at least in part independent by the peripheral trigeminal arm involvement, possibly mediated by the recurrent suppression of a central inhibitory modulation of trigeminal nuclei neurons and ultimately leading to the transmission of even ordinary and usually not perceivable trigeminal ''noise'' signals. This perspective fully complies with the concept that, besides the countless research efforts, no evidence has ever been found supporting a defined ''pathology'' distinguishing migraine from healthy individuals [35].…”

Effect of cortical spreading depression on basal and evoked traffic in the trigeminovascular sensory system

“…The experiments reported here [part of a previously foreshadowed programme (11)] show that CSD -which could be either a trigger or a symptom of migraine (or both) -can generate sensory traffic in second-order sensory neurons independent of the generation of traffic in the first-order neurons which impinge upon them. These conclusions are fairly robust, but are subject to some limitations, summarized as: the experiments were conducted in anaesthetized rats; it is not known whether CSD produces pain in rats and; it is not known whether the neurons involved in this study are the same types of neurons as those involved in the perception of migraine pain in humans.…”

Calcitonin Gene-Related Peptide (CGRP): A New Target for Migraine

“…These include inflammatory mediators and agents that are released during neurogenic inflammation, cortical spreading depression (CSD), or both (22). According to an alternative central mechanism, defective processing in the CNS could lead to the perception of non-noxious trigeminovascular input as painful (23). Within the trigeminal nerve, the most abundant neuropeptide is CGRP, which is expressed in 35--50% of neurons in the trigeminal ganglia (24).…”