Allodynia in Migraine: Association with Comorbid Pain Conditions

Gretchen E. Tietjen, MD; Jan L. Brandes, MD; B. Lee Peterlin, DO; Arnolda Eloff, MD; Rima M. Dafer, MD, MPH; Michael R. Stein, MD; Ellen Drexler, MD; Vincent T. Martin, MD; Susan Hutchinson, MD; Sheena K. Aurora, MD; Ana Recober, MD; Nabeel A. Herial, MD, MPH; Christine Utley, MSN, CNP; Leah White, MPH; Sadik A. Khuder, MPH, PhD


Headache. 2009;49(9):1333-1344. 

In This Article

Abstract and Introduction


Background.—Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous system sensitization. Several chronic pain syndromes and mood disorders are comorbid with migraine. In this study we examine the relationship of migraine-associated CA with these comorbid conditions. We also evaluate the association of CA with factors such as demographic profiles, migraine characteristics, and smoking status that may have an influence on the relationships of CA to pain and mood.
Methods.—Data are from a cross-sectional multicenter study of comorbid conditions in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a physician based on the International Classification of Headache Disorders-II criteria. Participants completed a self-administered questionnaire ascertaining sociodemographics, migraine-associated allodynia, physician-diagnosed comorbid medical and psychiatric disorders, headache-related disability, current depression, and anxiety.
Results.—A total of 1413 migraineurs (mean age = 42 years, 89% women) from 11 different headache treatment centers completed a survey on the prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the participants. Sixty percent of the study population reported at least one migraine-related allodynic symptom, 10% reported ≥4 symptoms. Symptoms of CA were associated with female gender, body mass index, current smoking, presence of aura, chronic headaches, transformed headaches, severe headache-related disability, and duration of migraine illness from onset. The prevalence of self-reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also associated with symptoms of CA. Adjusted ordinal regression indicated a significant association between number of pain conditions and severity of CA (based on symptom count). Adjusting for sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions (odds ratio = 3.03, 95% confidence interval: 1.78–5.17), and 2 pain conditions (odds ratio = 2.67, 95% confidence interval: 1.78–4.01) when compared with those with no comorbid pain condition.
Conclusion.—Symptoms of CA in migraine were associated with current anxiety, depression, and several chronic pain conditions. A graded relationship was observed between number of allodynic symptoms and the number of pain conditions, even after adjusting for confounding factors. This study also presents the novel association of CA symptoms with younger age of migraine onset, and with cigarette smoking, in addition to confirming several previously reported findings.


Repeated or prolonged noxious stimulation may lead to sensitization, a term describing increased neuronal responsiveness, within the central nervous system.[1] Through altered functions of chemical, electrophysiological, and pharmacological systems, central sensitization is manifested by the clinical phenomenon of allodynia.[2] Cutaneous allodynia (CA) refers to the perception of pain or discomfort in response to non-noxious thermal and mechanical stimuli applied to normal skin.[3] Studies using sensory testing, questionnaire data, or both, suggest that up to 80% of migraine patients experience CA during an acute attack.[3–6] The putative underlying mechanism of CA in migraine is central sensitization of second order neurons of the trigeminal nucleus caudalis, or third order neurons in the thalamus.[3] These central neurons receive convergent intracranial (dural and meningeal blood vessels) and extracranial (skin and hair follicle) sensory input accounting for the link of migraine headache and cutaneous discomfort.[3] Among migraine sufferers, allodynia is more commonly reported in persons with frequent headache,[6] and long duration of the disorder,[7] suggesting that it results from repeated sensitization of central pain pathways over time. The theory of ongoing sensory neuronal sensitization in the trigeminal pain pathways, is supported by the finding of allodynia extending into the interictal period,[8] as well as the increased prevalence in persons with transformed migraine.[9–11] The role of cortical hyperexcitablilty in the process remains uncertain as there are conflicting data on the prevalence of allodynia in migraine with aura compared with migraine without aura.[4,9,11,12]

Many persons with migraine suffer from other pain conditions implicating diffuse changes in the function of the nociceptive nervous system. For example, fibromyalgia (FM), irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), and endometriosis (EM) have all been linked to central sensitization,[13] as well as to migraine.[14] Depression and anxiety occur with high frequency with chronic pain conditions, including migraine, although the mechanism is uncertain.[15] The objective of this headache clinic study was to examine the relationship of migraine-associated cutaneous allodynic symptoms with comorbid conditions, including pain syndromes and mood disorders. We also evaluate the association of CA and other factors, such as demographic profiles, headache characteristics, and smoking history, which may have an influence on the relationships of CA to pain and mood.


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