Reyes Nicholas, Huang Jaxon J, Choudhury Anjalee, Pondelis Nicholas, Locatelli Elyana V, Felix Elizabeth R, Pattany Pradip M, Galor Anat, Moulton Eric A
Surgical Services, Miami Veterans Administration Medical Center, Miami, FL, United States.
Bascom Palmer Eye Institute, University of Miami, Miami, FL, United States.
Front Neurosci. 2023 Jun 19;17:1202341. doi: 10.3389/fnins.2023.1202341. eCollection 2023.
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.
Twelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. 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. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed.
At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," = 6), while 50% had equivalent ( = 3) or increased ( = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not.
BoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.
使用功能磁共振成像（fMRI）研究A型肉毒杆菌毒素（BoNT-A）对慢性眼痛患者疼痛和畏光潜在神经机制的影响。
从迈阿密退伍军人事务眼科诊所招募了12名患有慢性眼痛和对光敏感的受试者。纳入标准为：（1）慢性眼痛；（2）在回忆期超过1周存在眼痛；（3）存在畏光症状。所有个体在BoNT-A注射前和注射后4 - 6周进行眼表检查以获取泪液参数。采用事件相关fMRI设计，在两次fMRI扫描期间向受试者呈现光刺激，一次在BoNT-A注射前，一次在注射后4 - 6周。每次扫描后受试者报告光诱发的不适感评分。分析全脑对光刺激的血氧水平依赖（BOLD）反应。
在基线时，所有受试者报告光刺激会引起不适感（平均：70.8±32.0）。BoNT-A注射后4至6周，不适感评分下降（48.1±33.6），但变化不显著。在个体水平上，与基线相比，50%的受试者对光刺激的不适感评分降低（“反应者”，n = 6），而50%的受试者不适感评分相当（n = 3）或增加（n = 3）（“无反应者”）。在基线时，反应者和无反应者之间存在一些差异；与无反应者相比，反应者对光的基线不适感评分更高，抑郁症状更严重，且更频繁使用抗抑郁药和抗焦虑药。基线时的组分析显示，双侧初级体感皮层（S1）、双侧次级体感皮层（S2）、双侧前岛叶、扣带前回、中央扣带回皮质（MCC）、双侧额极、双侧小脑半球小叶VI、蚓部、双侧小脑脚I和II以及视觉皮层出现光诱发的BOLD反应。BoNT-A注射显著降低了双侧S1、S2皮层、小脑半球小叶VI、小脑脚I和左侧小脑脚II的光诱发BOLD反应。BoNT-A反应者在基线时显示出三叉神经脊束核的激活，而无反应者则没有。
BoNT-A注射可调节一些慢性眼痛患者光诱发的疼痛相关脑系统激活和畏光症状。这些效应与负责处理疼痛的感觉辨别、情感维度和运动反应区域的激活减少有关。
