Pain and stress cycle and the role of aspirin (acetylsalicylic acid): an assessment through a 5A framework

Stress and pain are biologically interconnected in a mutually reinforcing cycle. Stress may precipitate and exacerbate episodes of acute headache disorders such as migraine and tension-type headache (TTH), which rank among the most prevalent, disabling conditions worldwide. Timely and effective management of stress-related acute headache disorders can restore function and support engagement in longer-term management strategies. Over-the-counter (OTC) analgesics, given their favorable benefit-risk profile, may be an appropriate first-line treatment option for selected patients. However, their real-world benefit depends on factors beyond efficacy/safety, including determinants of access and use and patient-specific considerations such as symptom severity, expected frequency and duration of use, and risk of adverse effects. This framework-based narrative review explores a 5A model (Affordability, Availability, Accessibility, Acceptability, and Appropriateness) to assess the real-world suitability of OTC options. We used acetylsalicylic acid (ASA) as an example and conducted targeted literature searches across five domains, focusing on acute migraine and episodic TTH, and including accompanying neck/shoulder symptoms where relevant. Available evidence supports the clinical efficacy of ASA in acute migraine and episodic TTH, while real-world studies report favorable tolerability and patient-reported effectiveness. ASA remains widely available in diverse formulations, readily accessible as an OTC medicine, affordable compared with prescription and other OTC alternatives, and generally acceptable to patients, as demonstrated by its long-standing use. Its identification as one of the most cost-effective evidence-based interventions for migraine in population-level analyses further supports its appropriateness for selected patients within the 5A framework. As applied to ASA, the 5A framework illustrates how these five dimensions can be considered together to inform treatment decisions. We propose this framework to help patients and healthcare providers weigh the relative advantages and limitations of OTC analgesics and support safe, timely, clinically appropriate, and cost-effective self-care.