Effects of Botulinum Toxin Type A on the Nociceptive and Lemniscal Somatosensory Systems in Chronic Migraine: An Electrophysiological Study

Gabriele Sebastianelli, Francesco Casillo, Antonio Di Renzo, Chiara Abagnale, Ettore Cioffi, Vincenzo Parisi, Cherubino Di Lorenzo, Mariano Serrao, Francesco Pierelli, Jean Schoenen, Gianluca Coppola, Gabriele Sebastianelli, Francesco Casillo, Antonio Di Renzo, Chiara Abagnale, Ettore Cioffi, Vincenzo Parisi, Cherubino Di Lorenzo, Mariano Serrao, Francesco Pierelli, Jean Schoenen, Gianluca Coppola

Abstract

(1) Background: OnabotulinumtoxinA (BoNT-A) is a commonly used prophylactic treatment for chronic migraine (CM). Although randomized placebo studies have shown its clinical efficacy, the mechanisms by which it exerts its therapeutic effect are still incompletely understood and debated. (2) Methods: We studied in 15 CM patients the cephalic and extracephalic nociceptive and lemniscal sensory systems using electrophysiological techniques before and 1 and 3 months after one session of pericranial BoNT-A injections according to the PREEMPT protocol. We recorded the nociceptive blink reflex (nBR), the trigemino-cervical reflex (nTCR), the pain-related cortical evoked potential (PREP), and the upper limb somatosensory evoked potential (SSEP). (3) Results: Three months after a single session of prophylactic therapy with BoNT-A in CM patients, we found (a) an increase in the homolateral and contralateral nBR AUC, (b) an enhancement of the contralateral nBR AUC habituation slope and the nTCR habituation slope, (c) a decrease in PREP N-P 1st and 2nd amplitude block, and (d) no effect on SSEPs. (4) Conclusions: Our study provides electrophysiological evidence for the ability of a single session of BoNT-A injections to exert a neuromodulatory effect at the level of trigeminal system through a reduction in input from meningeal and other trigeminovascular nociceptors. Moreover, by reducing activity in cortical pain processing areas, BoNT-A restores normal functioning of the descending pain modulation systems.

Keywords: botulinum toxin type A; central sensitization; lemniscal system; migraine; pain; peripheral sensitization; trigemino-cervical complex.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
1st block amplitudes and habituation slopes of the ipsi- and contralateral nociceptive blink reflex (nBR) and of the nociceptive trigemino-cervical reflex (nTCR) before (T0), 1 month (T1) and 3 months (T3) after the BoNTA injections. Means ± standard error of means. * = p < 0.05 vs. T0.
Figure 2
Figure 2
1st block amplitudes and habituation slopes of the trigeminal pain-related cortical evoked potential (PREP) and the upper limb somatosensory evoked cortical potential (SSEP) before (T0), 1 month (T1) and 3 months (T3) after the BoNTA injections. Means ± standard error of means. * = p < 0.05 vs. T0.
Figure 3
Figure 3
Flow chart of the study’s visits and recording sessions. Chronic migraine patients were recorded just before (T0), 1 month (T1) and 3 months (T3) after one session of BoNT-A injections. The nociceptive trigeminal system was tested through the recording of nociceptive blink reflex (1), trigemino-cervical reflex (2), and pain-related evoked potentials (3), during the percutaneous electrical stimulation of the innervation territory of the supraorbital nerve at the forehead. The non-painful lemniscal sensory systems were investigated through somatosensory evoked potentials (4) elicited by electrically stimulating the right median nerve at the wrist (Created with BioRender.com, accessed on 23 December 2022).

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