Experimental evidence of a functional relationship within the brainstem trigeminocervical complex in humans

Abstract

The existence of a trigeminocervical complex has been suggested based on animal data, but only indirect evidence exists in humans. We investigated the functional relationship between the trigeminal and the occipital region by stimulating one region and measuring electrical pain thresholds (EPTs) of the corresponding opposite region. This study consists of 2 single-blinded, randomised protocols. Forty healthy participants were recruited in the propaedeutic protocol I. Electrical pain thresholds were measured on the V1 and the greater occipital nerve (GON) dermatome bilaterally as well as on the left forearm longitudinally before and after application of topical capsaicin. Protocol II was then online preregistered, and, additionally, the ipsilateral trigeminal dermatomes V2 and V3 were tested. Greater occipital nerve stimulation increased the EPT ipsilateral at V1 after 20 minutes (P 5 0.006) compared with baseline, whereas trigeminal stimulation increased the EPT at the ipsilateral (P 5 0.023) as well as the contralateral GON (P 5 0.001) after capsaicin application. Protocol II confirmed these results and additionally showed that GON stimulation with capsaicin increased EPTs ipsilateral at all 3 trigeminal dermatomes and that trigeminal stimulation on V1 led to an ipsilateral increase of EPTs at GON, V2, and V3. Our data suggest a strong functional interplay between the trigeminal and occipital system in humans. The fact that the stimulation of one of these dermatomes increases the EPT of the respective other nerve could be explained by segmental inhibition on the brainstem level.

Electroacupuncture alleviates orofacial allodynia and anxiety-like behaviors by regulating synaptic plasticity of the CA1 hippocampal region in a mouse model of trigeminal neuralgia

“…The trigeminal branches include the ophthalmic nerve (zone V1), the maxillary nerve (zone V2), and the mandibular nerve (zone V3; Figure 1A ; Basedau et al, 2022 ). It has been reported that the pT-ION model exhibits primary nociceptive hypersensitivity not only in zone V2 but also secondary nociceptive hypersensitivity in zone V3 ( Cui et al, 2020b ; Hu et al, 2020 ).…”

A Review of Current Perspectives on Facial Presentations of Primary Headaches

“… 46 , 47 It has recently been demonstrated that the stimulation of the V1 dermatome via capsaicin was able to modulate the pain threshold in the V2, V3, and GON dermatome; similarly, stimulation at the GON was able to change the pain threshold on all three branches of the trigeminal nerve, but with a stronger effect on V1, compared to V2/V3. 48 This study provided evidence that the functional interaction between different branches of the trigeminal nerve takes place at the pontomedullary level. We have demonstrated that the functional connection between the limbic system and the ophthalmic branch exists in migraine and explains the attack-like behavior; 49 , 50 this functional connection explains why such attack-like pains are predominately in the head.…”

Additional effects of pain neuroscience education combined with physiotherapy on the headache frequency of adult patients with migraine: A randomized controlled trial

“…Indeed, more severe migraine presentations are associated with more musculoskeletal findings but the difference between chronic and episodic migraine is less pronounced than between migraine patients and healthy participants (10,12). Head pain referral during manual palpation of upper cervical structures (13–15) points towards a connection between the occipital, upper cervical and trigeminal nerves, indicating a convergence of afferences at brainstem level within the trigeminocervical complex (16,17). A reciprocal connection can be inferred from preliminary data indicating a reduced headache frequency after physiotherapy focusing on cervical musculoskeletal structures (18,19), but there is currently no evidence from methodologically rigorous randomized controlled trials.…”