Discussion
cutaneous allodynia, Allodynia, allodynia, psychiatric, headache, migraine, migraine-related
MIGRAINE, CHRONIC MIGRAINE, MIGRAINE VARIANT
This study shows that the absence of cutaneous allodynia is predictive for a good outcome after withdrawal therapy in patients with chronic migraine with medication overuse. The predictive value was even more pronounced when comparing with extracephalic allodynia, which is indicative of trigeminothalamic involvement. Our findings further suggest a migraine specific relationship because allodynia was only a strong predictor for migraine-related outcome measures.These findings are relevant to clinical practice and current treatment concepts and expectations. Chronic migraine is a highly disabling migraine variant, in which the majority of patients overuse acute headache medication [The association between cutaneous allodynia, and its spatial distribution, and response to treatment may have additional value for current pathophysiological concepts on migraine chronification. The predictive value for failure on treatment was most pronounced for extracephalic allodynia, which is considered indicative for thalamic involvement [In our study, mechanical allodynia was associated with change in monthly migraine days, as opposed to thermal allodynia. This finding appears to be not due to a lack of power in the thermal allodynia group as both sample sizes were equal. So while we cannot exclude that with more power their might be a difference as well for thermal allodynia, these findings would suggest that mainly mechanoreceptors, such as the low threshold Aβ fibres and C-type mechanoreceptors [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. Furthermore, while providing interesting avenues that are worth exploring and potentially creating a better understanding of the pathophysiological mechanisms involved in allodynia, we need to consider that while consistent across different migraine outcomes, our findings on allodynia caused by specific types of stimuli are based on a limited amount of participants. It would be worthwhile to evaluate our findings in a larger cohort. Moreover, the Allodynia Symptom Checklist is a self-reporting questionnaire and as such subjected to subjectivity. As such our measurements might therefore not be as reliable as the physiological assessment with QST, especially in assessing thermal allodynia, and possibly to a lesser extent mechanical allodynia. Nevertheless, as QST requires specialized equipment, training, and testing, is time consuming and costly, our evaluation is by far more applicable in clinical practice. Additionally, 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 outcome measures [