Author Response: Characterizing Opioid Use in a US Population With Migraine: Results From the CaMEO Study

We thank Dr. Blumenfeld for his comments on our article.1 In our manuscript, we acknowledged that—in this cross-sectional analysis—we cannot determine the causal sequence that links opioid use to migraine features, such as severe disability, allodynia, and comorbid depression and anxiety. People with treatment-refractory headaches may be given opioids in an effort to relieve pain. In animal models, prolonged exposure to opioids may produce latent sensitization and long-lasting alterations in descending pain modulation; this work provides potential mechanistic links for opioid use leading to worsening of headaches.2 To resolve the causal sequence, longitudinal studies with close follow-up using daily diaries are needed. Unlike opioids and triptans, ubrogepant does not produce latent sensitization, providing hope that gepants may not exacerbate headache.2,3 Having acute treatments that do not lead to headache exacerbation may be helpful in longitudinal studies.

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