Assessing the Effect of Botulinum Toxin A in Individuals with Chronic Ocular Pain and Photophobia Using fMRI

Abstract

Purpose : To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain.

Methods : 12 subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: 1) average ocular pain rating over 1 week recall ≥ 1 (range 0-10); and 2) presence of photophobia (“Eye pain provoked or increased by light” score of ≥ 1 during the past 24 hours, range 0-10). Demographics, co-morbidities, and medication use were captured from all participants. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Unpleasantness ratings evoked by light (Verbal Rating Scale: 0-100) were reported by subjects after each scan. Blood oxygen level dependent (BOLD) responses to light stimuli were analyzed in brain regions related to pain processing.

Results : At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8±32.0). 4-6 weeks after BoNT-A injection, 50% of subjects had improved unpleasantness scores in response to light stimulation compared to baseline (responders, n=6) while the remaining reported maintained, n=3, or increased, n=3, unpleasantness (non-responders). Responders were more likely to report depressive symptoms and use antidepressants and anxiolytics compared to non-responders. Group analysis at baseline displayed light evoked BOLD responses in various brain regions including bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, frontal pole, bilateral cerebellar hemispheric lobules I-VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, bilateral S2 cortices, bilateral cerebellar hemispheric lobule VI, bilateral cerebellar crus I, and left cerebellar crus II.

Conclusions : BoNT-A injections modulate photophobia symptoms in some individuals. These effects may be driven by decreased activation in areas responsible for processing the affective (S2, cerebellar hemispheric lobule VI, crus I and II), sensory-discriminative (S1 and S2) dimensions, and motor (cerebellar vermis and bilateral lobule V) responses to pain.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.