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. 2025 Apr 5;25(1):145.
doi: 10.1186/s12883-025-04147-y.

Trigemino-autonomic activation in a human trigeminal pain model

Stefan Evers  1   2 , Achim Frese  3   4 , Patrick Hornberg  5 , Oliver Summ  6
Affiliations

Trigemino-autonomic activation in a human trigeminal pain model

Stefan Evers et al. BMC Neurol. .

Abstract

Background: Autonomic symptoms are mandatory for making the diagnosis of a trigemino-autonomic cephalalgia (TAC). These symptoms can occasionally also occur in migraine and facial pain disorders. This leads to the question whether the trigeminal pain itself can induce autonomic symptoms also in healthy subjects.

Methods: We enrolled healthy subjects without a history of migraine or a TAC and provoked severe trigeminal pain by injection of 0.05 ml capsaicin (0.01%) into the right forehead. Autonomic symptoms occurring at the right eye or right nostril were registered until they disappeared. We also calculated an autonomic score for the frequency and duration of autonomic symptoms in an individual.

Results: We enrolled 60 healthy volunteers (30 male, 30 female; mean age 28 +/- 5 years). All but two subjects developed at least one autonomic symptom after injection of capsaicin. One minute after injection, the pain was rated as 9.2 +/- 1.1 and 8.5 +/- 1.2 (scale from 0 to 10) in female and male subjects, respectively. The autonomic score was 4.4 +/- 1.6 and 1.7 +/- 0.9 for female and male subjects, respectively. All differences between female and male subjects were significant. Pain rating and autonomic score showed a significant positive correlation which remained significant even after adjusting for sex.

Conclusions: Severe trigeminal pain was accompanied by autonomic symptoms in almost all subjects in this experiment. The pain rating and the severity of autonomic symptoms were significantly higher in female subjects than in male. The higher the pain the more severe was this autonomic activation. We conclude that activation of autonomic symptoms is an unspecific consequence of severe trigeminal pain. This does, however, not exclude the possibility that primary headache disorders might have an independent anatomic pathway to induce autonomic symptoms because these symptoms can, although very rarely, also occur without pain.

Keywords: Capsaicin; Cluster headache; Trigemino-autonomic symptoms.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol was approved by the local ethics committee of the University of Münster. All subjects gave written informed consent following a detailed explanation of the procedure. The experiment was performed according to the Declaration of Helsinki for performing medical research involving human participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

References

    1. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases. Brain. 1997;120:193–209. - PubMed
    1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edn. Cephalalgia. 2018;38:1-211. - PubMed
    1. Goadsby PJ, Edvinsson L, Ekman R. Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol. 1990;28:183–7. - PubMed
    1. Barbanti P, Fabbrini G, Pesare M, Vanacore N, Cerbo R. Unilateral cranial autonomic symptoms in migraine. Cephalalgia. 2002;22:256–9. - PubMed
    1. Barbanti P, Aurilia C, Dall’Armi V, Egeo G, Fofi L, Bonassi S. The phenotype of migraine with unilateral cranial autonomic symptoms documents increased peripheral and central trigeminal sensitization. A case series of 757 patients. Cephalalgia. 2016;36:1334–40. - PubMed

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