Noninvasive cranial suture stimulation: exploring the functional extracranial–intracranial trigeminal fibre connection in humans

Recent evidence suggests that cranial sutures could serve as conduits for nociceptive transmission from extracranial to intracranial fibres, potentially influencing headache pathophysiology. Animal studies indicate extracranial stimulation affects dural nerve activity, and suture-targeted therapies like botulinum toxin show efficacy in chronic migraine. However, the role of the "suture pathway" in human headache generation remains unclear. This study investigates whether extracranial stimulation over cranial sutures induces more intracranial activation, ie, headache generation, than stimulation at nonsutural sites. Sixty healthy participants from 3 cohorts (n = 20 each) received noninvasive capsaicin or electrical stimulation at sutural and nonsutural sites in a pseudorandomised parallel-group crossover design. Headache occurrence, intensity, and duration were compared. The 3 study cohorts were comparable in terms of the sex and age distribution (50% being female, with an average age between 25 and 30 years). After stimulation, the incidence of headaches at the suture site point was 35%, 60%, and 25% in cohorts 1, 2, and 3, respectively. No significant difference was found between sutural and nonsutural sites (P > 0.05 in all 3 cohorts). The functional relevance of the sutural pathway remains inconclusive in humans. Although extracranial stimulation indeed may result in headache, this effect appears to be independent of the stimulation sites. Adjacent structures, including epicranial muscles, may modulate the headache induction rate. The functional role of the connection may be different in patients with headache than in healthy controls. Future research should explore these mechanisms using an optimised stimulation protocol, with a focus on patients with headache.