Effect of circadian rhythm on the pain associated with preventive onabotulinumtoxinA injections for migraines

The aim of our research was to assess if the pain and discomfort following each quarterly onabotulinumtoxinA (BTA) injection given to prevent daily headaches/migraines is circadian time-dependent so as to determine the best administration time for least discomfort and minimal follow-up pain. A total of 61 diurnally active patients with a medical history of chronic migraine headaches and undergoing preventative BTA injection therapy for the first time were enrolled in the study. Patients were randomly assigned to morning or afternoon clinics, but had the ability to choose within the assigned clinic the injection time that best fits their schedule. 155 units of BTA was administered by following the standardized PREEMPT injection protocol. Patients reported the typical time of sleep onset and wakeup time for the week prior to injections. Patients then self-reported three levels of pain in the head and neck area: prior to BTA injections, immediately after, and 24 h after BTA injections. This was carried out by marking the pain level on 100 mm visual analog pain scale. Descriptive summaries were frequencies and percentages for categorical data and medians and quartiles for continuous variables. Demographic variables of gender, race, and age were tested using Chi-Square. Groups of morning versus afternoon patients were compared using the non-parametric Wilcoxson's Rank Sum Tests and student T tests. All analysis was done in SAS for Windows Version 9.4. 38 (62%) patients were injected during morning clinic and 23 (38%) during afternoon clinic. There was no difference in gender, race, and age variables between morning and afternoon patients. 67% of the patients experienced increased pain following the initial injection. Higher pain score was more frequent following morning than afternoon injections (78% vs. 50%, p = .021). The 24 h post-injection pain level was also significantly higher in patients injected in the morning than afternoon (64% vs. 28%, p = .024). Performing BTA injections for migraine prevention during the morning was associated with significantly more treatment-related discomfort, both immediately and 24 h after injection. Scheduling diurnal active patients with stable circadian sleep/wake routine for afternoon BTA injections appears beneficial for decreasing treatment-related discomfort and potentially increase compliance to therapy.