Page 120 - The clinical aspects and management of chronic migraine Judith Anne Pijpers

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Chapter 6
Strengths of this study are the large well-defined, representative chronic migraine population, with a high follow-up rate after withdrawal therapy and detailed information on headache characteristics, allodynia and psychiatric comorbidity. Due to detailed and prospective headache diaries, a distinction in migraine days and headache days could be made. The division in subtypes of cutaneous allodynia have never been studied related to chronic migraine in a longitudinal design. However, the subdivision on spatial distribution also has limitations. The Allodynia Symptom Checklist does not discern ipsilateral cephalic allodynia (second order neurons) and contralateral cephalic allodynia (third order neurons), as this cannot be reliably assessed in a questionnaire. Due to the division into different subgroups and the limited number of symptoms in the questionnaire, we used the criterion of at least one symptoms present for each subcategory, and not two or more as for the overall allodynia scores. Secondly, the study was part of a clinical trial on the effect of botulinum toxin A versus placebo, and we cannot fully rule out potential influence of the trial on the results. However, botulinum toxin A did not have additional benefit over placebo on all outcomes measures 17, and adjusting for botulinum toxin A treatment did not alter the associations between (subtypes of) cutaneous allodynia and migraine-related outcome. Theoretically, the injection of any fluid (independently medication or saline) might cause a general immune reaction and influence results as immune cells are involved in hypersensitivity. Animal studies suggest a different immune-mediated pathway for male and female 39, which might explain the difference in prevalence of cutaneous allodynia in male and female chronic migraine patients. Nevertheless, the association between cutaneous allodynia and response was adjusted for gender, and remained unchanged when analysis was rerun in female patients only making immune mediated influences of injection very unlikely.
This study shows that cutaneous allodynia, an important marker for central sensitization, is a predictor for response to withdrawal therapy in patient with chronic migraine and medication overuse. Allodynia might be an important predictor for treatment response in chronic migraine in general. Furthermore, considering subtypes of cutaneous allodynia, especially extracephalic allodynia and mechanical allodynia, enhances the predictive value for migraine-related outcomes and might help to increase insight in the mechanisms of chronification in migraine.