Generalized Pain Sensitization and Endogenous Oxytocin in Individuals With Symptoms of Migraine: A Cross‐Sectional Study

Objective The current study examined pain and neurogenic inflammation responses to topical capsaicin during the interictal period (between headache) and their relationship with plasma oxytocin in individuals with migraine. Background Individuals with migraine can experience generalized (extracephalic) hyperalgesia, which can persist even between headache attacks. Elevated levels of plasma and cerebrospinal fluid oxytocin have been observed during migraine attacks, oxytocin levels being positively associated with the intensity of migraine symptoms. However, whether oxytocin plays a role in the mechanisms of generalized pain sensitization and neurogenic inflammation during the interictal period has not been studied yet. Understanding migraineurs' interictal pain phenotype and endogenous oxytocin might help identify individuals who would benefit from intranasal oxytocin treatment. Methods Thirty‐two subjects with migraine and 26 healthy controls underwent pain testing. The current study compared capsaicin‐induced pain, central sensitization (areas of secondary mechanical allodynia and hyperalgesia), and neurogenic inflammation (capsaicin‐induced flare) responses on the nondominant volar forearm between migraineurs and healthy controls. Additionally, we studied plasma oxytocin levels and their relationship to migraine symptoms, experimental pain and affect. Results The results indicated a significant group effect (P = .019): Migraineurs reported greater capsaicin‐induced pain unpleasantness (M = 1.2, SD = 1.4) on a 0‐10 scale and showed larger areas of flare (LnM = 2.8, SD = 0.4) than healthy controls (M = 0.5, SD = 0.8; LnM = 2.6, SD = 0.4; ps .200), migraineurs. The oxytocin levels were elevated in migraineurs and accounted for 18% of the group difference in capsaicin‐induced pain unpleasantness. Within migraineurs, interictal oxytocin levels were negatively associated with psychological distress (Ps .074). Lastly, the results found no group difference in areas of secondary mechanical allodynia and hyperalgesia (Ps >.298). Conclusion The current study revealed that individuals with migraine exhibit enhanced extracephalic capsaicin‐induced pain unpleas