Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration

Abstract

Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients’ quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

Cortical and Subcortical Alterations in Medication Overuse Headache

“…Here, high resolution MPRAGE (1 mm 3 ) structural images and functional images (echo planar imaging sequence, repetition time 2.62 s, echo time 30 ms, flip angle 80°, field of view 220 × 220 mm 2 , 2 × 2 mm 2 in-plane resolution, 40 axial slices per volume with 2 mm slice thickness, and 1 mm gap) during the actual experiment were acquired in approximately 55 min. Further details on the MR parameters can be found elsewhere ( 18 – 20 ).…”

Headache Perception in an Epilepsy Patient with Neuromodulation by Anterior Thalamic Nuclei Deep Brain Stimulation: A Case Report

“…1a, c). Moreover, in patients who underwent VNS and topiramate treatment, [4][5][6] global reduction of the PASS-40 pain perception parameters was observed, regardless of the subscores (►Fig. 1c).…”

“…Furthermore, the thalamocortical loop also seems to be involved in the pathophysiology of migraine. 4,5 In animal models of epilepsy, VNS demonstrated a desynchronization of cortical electrical activity by modulation of the locus coeruleus as the putative mechanism of its antiepileptic effects. The pathways involved in the analgesic action of VNS in chronic headache, however, remain unclear.…”

Age-Dependent Anti-migraine Effects of Valproic Acid and Topiramate in Rats

“…In human, it was reported that intravenous administration of TPM attenuated the pain-related activity of parts of the thalamo-cortical network and increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex suggesting that TPM exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain ( Hebestreit and May, 2017 ). With the recent discovery of direct cortico-trigeminal inhibition from primary somatosensory cortex to TNC ( Castro et al, 2017 ), and the existence of direct TNC innervation from secondary somatosensory cortex ( Tashiro et al, 1983 ), it is speculated that TPM may activate that descending cortico-trigeminal inhibitory pathway, hence centrally suppressed the c-Fos expression in TCC of both pediatric and adult rats.…”