Cutaneous Allodynia in Migraine: A Narrative Review

Abstract

ObjectiveIn the present work, we conduct a narrative review of the most relevant literature on cutaneous allodynia (CA) in migraine.BackgroundCA is regarded as the perception of pain in response to non-noxious skin stimulation. The number of research studies relating to CA and migraine has increased strikingly over the last few decades. Therefore, the clinician treating migraine patients must recognize this common symptom and have up-to-date knowledge of its importance from the pathophysiological, diagnostic, prognostic and therapeutic point of view.MethodsWe performed a comprehensive narrative review to analyze existing literature regarding CA in migraine, with a special focus on epidemiology, pathophysiology, assessment methods, risk for chronification, diagnosis and management. PubMed and the Cochrane databases were used for the literature search.ResultsThe prevalence of CA in patients with migraine is approximately 60%. The mechanisms underlying CA in migraine are not completely clarified but include a sensitization phenomenon at different levels of the trigemino-talamo-cortical nociceptive pathway and dysfunction of brainstem and cortical areas that modulate thalamocortical inputs. The gold standard for the assessment of CA is quantitative sensory testing (QST), but the validated Allodynia 12-item questionnaire is preferred in clinical setting. The presence of CA is associated with an increased risk of migraine chronification and has therapeutic implications.ConclusionsCA is a marker of central sensitization in patients with migraine that has been associated with an increased risk of chronification and may influence therapeutic decisions.

Central Sensitization in Migraine: A Narrative Review

“…CA is a condition defined as perceptions of pain elicited by the application of nonpainful stimuli to normal skin; it has been observed in 60% of patients with migraine 59 and is even more prevalent in patients with chronic migraine (up to 90%). 60 The CS of trigeminovascular neurons has been implicated in the development of CA.…”

“…Other risk factors for CA include acute medication overuse and early age of migraine onset. 59 Longitudinal data over 2 years showed that CA is an independent risk factor for migraine chronification. 62 A study of resting-state functional connectivity showed that compared to migraine patients without ictal CA, migraine patients with ictal CA showed stronger functional connectivity of the periaqueductal gray and nucleus cuneiformis to other brainstem, thalamic, insular and cerebellar regions that participate in discriminative pain processing as well as higher order pain-associated regions, such as the frontal and temporal cortices.…”

“… 68 However, the role of CA in the triptan response is not conclusive. 59 Interestingly, the presence of CA predicted responsiveness to erenumab, a calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, along with male sex and baseline migraine frequency. 69 In contrast, a subanalysis of a double-blind, randomized, placebo-controlled study, showed that the efficacy of erenumab in reducing monthly migraine days and acute migraine-specific medication days in chronic migraine patients was not affected by the presence of moderate to severe CA.…”

The putative role of trigemino-vascular system in brain perfusion homeostasis and the significance of the migraine attack

“…The nature of this predisposition to migraine pain is probably multifactorial and polygenic and it can vary between different individuals and within the same individual over time. It could be linked to the multiple peculiarities of the “migraine brain” [ 81 ], to a lower allodynic threshold [ 82 ], might be modulated by estrogen fluctuations in female sex, and can explain the observation that the CGRP or PACAP induce a migraine attack only in migraine patients [ 14 , 15 ]. In this perspective, migraine remains a “primary” disease that afflicts a minority of the individuals carrying a sinus stenosis-associated deranged intracranial pressure control, which also shares the ability to trigger a migraine attack at relatively low trigemino-vascular activation threshold.…”

Chronic Migraine as a Primary Chronic Pain Syndrome and Recommended Prophylactic Therapeutic Options: A Literature Review

“…The prevalence of cutaneous allodynia in patients with migraine is rather high, estimated to be between 40–70%. The presence of allodynia is a marker of central sensitization in migraineurs and is associated with an elevated risk for chronification [ 152 ]. In addition, with its dual origin from two distinct arms of diseases (i.e., chronic pain syndromes and primary headache disorders), CM is a highly prevalent condition, having a great socio-economic impact and posing an individual burden.…”