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Sumatriptan prevents central sensitization specifically in the trigeminal dermatome in humans
Author(s) -
Peng KuanPo,
Jürgens Tim,
Basedau Hauke,
Ortlieb Luise,
May Arne
Publication year - 2022
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.2027
Subject(s) - sumatriptan , triptans , dermatome , zolmitriptan , anesthesia , medicine , hyperalgesia , migraine , sensitization , cluster headache , pharmacology , nociception , agonist , receptor , immunology
Background The exact mechanism and site of action of triptans in aborting migraine attacks remain under debate. We hypothesized that the clinical efficacy of triptans lies in aborting central sensitization and focused on the question of why triptans are headache specific, that is highly effective in migraine and cluster headache and ineffective in extracephalic pain. Methods Forty healthy participants were enrolled in this double‐blinded, randomized, placebo‐controlled study. The effect of sumatriptan ( n = 20) versus placebo ( n = 20) was investigated in a trigeminal (V1) versus an extracephalic dermatome (forearm) using a topical capsaicin sensitization model. Capsaicin‐induced primary and secondary hyperalgesia were evaluated using quantitative sensory testing. Results After capsaicin application, primary hyperalgesia developed in both the sumatriptan and placebo groups in both dermatomes. However, sumatriptan exclusively prevented secondary hyperalgesia in the V1 dermatome but not on the forearm. Placebo exerted no effects on secondary hyperalgesia in both trigeminal and extracephalic dermatomes. Additionally, sumatriptan reduced the flare size exclusively in the V1 dermatome. Conclusions Our data suggest that sumatriptan reduces central sensitization (secondary hyperalgesia) without modulating peripheral sensitization (primary hyperalgesia) in a human pain model of capsaicin‐induced sensitization. Moreover, despite a systemic administration of sumatriptan, the modulatory effects are trigeminal specific, echoing the clinical effect of triptans in aborting headaches, but not extracephalic pain. Significance Our data suggest that triptans exert their efficacy by suppressing central sensitization. By revealing a dermatome‐specific modulation, our study demonstrates a previously unrecognized interaction between the pharmacodynamics of triptans and the trigeminal nociceptive system that provides new insight into how triptans may work in aborting headache attacks.