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

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.

Quantitative and Qualitative Pain Evaluation in Response to OnabotulinumtoxinA for Chronic Migraine: An Observational Real-Life Study

“…Therefore, a detailed quantitative and qualitative assessment of pain after the first OBT-A cycle would allow a more comprehensive and rapid evaluation of its efficacy and should be implemented when prescribing other treatment regimens. Nevertheless, we also observed a progressive increase in OBT-A's beneficial effects, possibly as a consequence of gradual central de-sensitization, allowing an increase in the pain threshold [23,50].…”

“…OnabotulinumtoxinA also decreases the insertion of pain-sensitive ion channels into the synaptic membranes of nociceptive neurons, resulting in reduced sensory neuron excitability. This inhibition of peripheral sensory fiber activation antidromically decreases the rate of pain signaling directed from the dura to the spinal trigeminal nucleus, which in turn hinders the establishment of hyperexcitability (i.e., central sensitization) of the neural networks involved in migraine pathophysiology [23]. This secondary effect on central sensitization is clinically evident in the progressive benefit observed in treated patients [16].…”

Early effect of onabotulinumtoxinA on EEG‐based functional connectivity in patients with chronic migraine: A pilot study

“…These data align with prior studies finding a rapid neuromodulator effect of botulinumtoxin-A (BTA) on the nociceptive networks at the central level. 15 These FC changes matched a clinical improvement in terms of both the number of days of migraine and overall disability, as measured by the MIDAS scores and the HIT-6 scale, although these electrophysiological correlations might reflect the improvement in migraine-related disability rather than a specific OBTA effect.…”

“…12,13 In contrast, when it comes to CM, studies investigating the central effects of OBTA are notably scarce and mainly limited to a few neurophysiological studies. 14,15 The study of FC is primarily based on radiological techniques such as functional magnetic resonance imaging (fMRI) or electrophysiological techniques such as high-density electroencephalography (HD-EEG). fMRI is based on indirect measures of neural activity, and its temporal resolution is suboptimal to capture brain dynamics, which occur in a few milliseconds.…”

Comparison of Efficacy of Botulinum Toxin Injection and Conventional Oral Drugs for Treatment of Refractory Migraine

“…Numerous studies attest to its efficacy and safety, resulting in FDA approval for the treatment of chronic migraines. Despite its demonstrated efficacy, precise mechanism of BoNT-A in migraine prophylaxis is still a subject of active investigation (10). Conventional oral medications, a broad category that includes triptans, nonsteroidal antiinflammatory drugs (NSAIDs), beta-blockers, antiepileptic drugs, and antidepressants, primarily seek to prevent migraines or reduce their severity.…”