Trigemino-autonomic activation in a human trigeminal pain model

• Published in: BMC neurology Vol. 25; no. 1; pp. 145 - 5
• Main Authors: Evers, Stefan, Frese, Achim, Hornberg, Patrick, Summ, Oliver
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.04.2025; BioMed Central; BMC
• Subjects: Adult; Autonomic Nervous System - physiopathology; Capsaicin; Care and treatment; Cluster headache; Diagnosis; Epidemiology; Female; Females; Headache; Headaches; Humans; Injection; Male; Migraine; Neuralgia, Trigeminal; Pain; Pain Measurement; Trigeminal Autonomic Cephalalgias - chemically induced; Trigeminal Autonomic Cephalalgias - diagnosis; Trigeminal Autonomic Cephalalgias - physiopathology; Trigeminal Nerve - physiopathology; Trigemino-autonomic symptoms; Young Adult; Germany; Capsaicin; Cluster headache; Trigemino-autonomic symptoms
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-025-04147-y

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. 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. 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. 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.