Study Characterizes Somatotopically Specific Differences in Pain Modulation in Interictal Migraine Phase

Woman with headache pain
One woman who is stressed or in pain from depression, anxiety or headache related health issues
Study findings suggest that pain modulation may be impaired in patients with migraine in the headache-free interval, despite an unaffected sensory profile.

Pain modulation may be impaired in patients with migraine in the headache-free interval, despite an unaffected sensory profile, according to a study in Pain. Researchers also found reduced pain inhibition may be specific to the trigeminal area.

Given the cyclic nature of migraine, and the variance in pain perception depending on migraine phase, researchers sought to determine whether patients with migraine already show altered pain modulation outside of the attack. Moreover, they aimed to determine if there was a difference between the offset analgesia (OA) response, a commonly used test paradigm to assess the function of descending pain modulation, in the trigeminal system compared to that in the somatic system.

This cross-sectional study included a total of 26 adults with episodic migraine with or without aura during the headache-free interval and 26 healthy controls. Researchers used an individualized OA paradigm that consisted of 3 stimulus offset trials which evaluated OA response at forehead (trigeminal) and forearm (extratrigeminal) test sites. Warm detection threshold, heat pain threshold, and Pain60 (individualized temperature of pain of 60 out of 100) were applied to identify differences in sensory perception between healthy controls and patients with migraine. The researchers also evaluated responses on questionnaires that assessed allodynia symptoms, disability, depression, and sleep quality.

In patients with migraine, there was a significant difference between offset trials and constant trials in the extratrigeminal area in contrast to the trigeminal area (P <.001). These same findings were observed in control participants (trigeminal: P =.001; extratrigeminal: P <.001), suggesting an impaired OA change in the trigeminal area. There was no significant difference in trigeminal area and extratrigeminal area in patients with migraine as well as trigeminal and extratrigeminal areas in healthy controls in terms of the warm detection threshold (P =.218), heat pain threshold (P =.805), and mechanical pain threshold (P =.571). The investigators reported a significant difference for mechanical detection thresholds (P <.001), which suggested differences between test sites.

A limitation of the study, according to the researchers, was the inability to determine whether the findings were specific to migraine or generalizable to trigeminal pain.

Related Articles

The investigators concluded that these findings suggest that patients with migraine have a disrupted OA that is distinct when compared to healthy controls. They also note that the “somatotopic organization of endogenous pain modulation has not been described before and may be specific for trigeminal pain syndromes or indeed for migraine.”


Szikszay TM, Adamczyk WM, Carvalho GF, May A, Luedtke K. Offset analgesia: somatotopic endogenous pain modulation in migraine. Pain. 2020;161(3):557-564.