Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia.
Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia.
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DOI：
10.3389/fnins.2023.1202341
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发表时间：
2023
影响因子：
4.3
通讯作者：
Moulton, Eric A.
中科院分区：
文献类型：
--
作者：
Reyes, Nicholas;Huang, Jaxon J.;Choudhury, Anjalee;Pondelis, Nicholas;Locatelli, Elyana V.;Felix, Elizabeth R.;Pattany, Pradip M.;Galor, Anat;Moulton, Eric A.
使用功能性磁共振成像 (fMRI) 检查 A 型肉毒杆菌毒素 (BoNT-A) 对慢性眼痛患者疼痛和畏光神经机制的影响。从迈阿密退伍军人事务部眼科诊所招募了 12 名患有慢性眼痛和光敏感性的受试者。纳入标准为：（1）慢性眼痛； (2)回忆起1周以上存在眼部疼痛； (3) 存在畏光。所有个体在注射 BoNT-A 之前和注射后 4-6 周均接受眼表检查以获取泪液参数。使用事件相关的功能磁共振成像设计，在两次功能磁共振成像扫描期间向受试者提供光刺激，一次是在注射 BoNT-A 之前，一次是在注射 BoNT-A 后 4-6 周。每次扫描后，受试者都会报告光引起的不愉快程度。分析了全脑血氧水平依赖性（BOLD）对光刺激的反应。在基线时，所有受试者都报告了光刺激的不愉快感（平均：70.8±32.0）。注射BoNT-A后4至6周，不愉快评分有所下降（48.1±33.6），但变化并不显着。在个人层面上，与基线相比，50% 的受试者对光刺激的不愉快程度降低（“有反应者”，n = 6），而 50% 的受试者对光刺激的不愉快程度相当（n = 3）或增加（n = 3）（“无反应者”）。在基线时，有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愉快评级更高，抑郁症状更严重，并且更频繁地使用抗抑郁药和抗焦虑药。基线组分析显示双侧初级体感（S1）、双侧次级体感（S2）、双侧前岛叶、副扣带回、中扣带皮层（MCC）、双侧额极、双侧小脑半球小叶 VI、蚓部、双侧小脑小腿的光诱发 BOLD 反应 I 和 II，以及视觉皮层。 BoNT-A 注射显着降低双侧 S1、S2 皮质、小脑半球小叶 VI、小脑小腿 I 和左小脑小腿 II 的光诱发 BOLD 反应。 BoNT-A 应答者在基线时表现出三叉神经脊髓核的激活，而无应答者则没有。 BoNT-A 注射可调节与疼痛相关的大脑系统的光诱发激活和一些慢性眼痛患者的畏光症状。这些影响与负责处理对疼痛的感觉辨别、情感、维度和运动反应的区域的激活减少有关。
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,” n = 6), while 50% had equivalent (n = 3) or increased (n = 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.
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