Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Département en Neuroscience, Centre de Recherche du CHUM, l'Université de Montréal, Montreal, QC, Canada.
Orphanet J Rare Dis. 2021 Jan 30;16(1):54. doi: 10.1186/s13023-021-01709-4.
Pain is a highly prevalent symptom experienced by patients across numerous rare musculoskeletal conditions. Much remains unknown regarding the central, neurobiological processes associated with clinical pain in musculoskeletal disease states. Fibrodysplasia ossificans progressiva (FOP) is an inherited condition characterized by substantial physical disability and pain. FOP arises from mutations of the bone morphogenetic protein (BMP) receptor Activin A receptor type 1 (ACVR1) causing patients to undergo painful flare-ups as well as heterotopic ossification (HO) of skeletal muscles, tendons, ligaments, and fascia. To date, the neurobiological processes that underlie pain in FOP have rarely been investigated. We examined pain and central pain mechanism in FOP as a model primary musculoskeletal condition. Central nervous system (CNS) functional properties were investigated in FOP patients (N = 17) stratified into low (0-3; 0-10 Scale) and high (≥ 4) pain cohorts using functional near-infrared spectroscopy (fNIRS). Associations among clinical pain, mental health, and physical health were also quantified using responses derived from a battery of clinical questionnaires.
Resting-state fNIRS revealed suppressed power of hemodynamic activity within the slow-5 frequency sub-band (0.01-0.027 Hz) in the prefrontal cortex in high pain FOP patients, where reduced power of slow-5, prefrontal cortex oscillations exhibited robust negative correlations with pain levels. Higher clinical pain intensities were also associated with higher magnitudes of depressive symptoms.
Our findings not only demonstrate a robust coupling among prefrontal cortex functionality and clinical pain in FOP but lays the groundwork for utilizing fNIRS to objectively monitor and central pain mechanisms in FOP and other musculoskeletal disorders.
疼痛是许多罕见肌肉骨骼疾病患者普遍存在的症状。目前对于肌肉骨骼疾病状态下与临床疼痛相关的中枢神经生物学过程知之甚少。进行性骨化性纤维发育不良（FOP）是一种遗传性疾病，其特征是身体残疾和疼痛严重。FOP 是由骨形态发生蛋白（BMP）受体激活素 A 受体 1 型（ACVR1）突变引起的，导致患者经历疼痛发作和异位骨化（HO），涉及骨骼肌肉、肌腱、韧带和筋膜。迄今为止，很少有研究调查 FOP 疼痛的神经生物学过程。我们以原发性肌肉骨骼疾病为模型，研究 FOP 中的疼痛和中枢疼痛机制。使用功能近红外光谱（fNIRS）对 FOP 患者（N = 17）进行分层，分为低疼痛（0-3；0-10 分制）和高疼痛（≥4）组，以研究中枢神经系统（CNS）功能特性。还使用一系列临床问卷的反应来量化临床疼痛、心理健康和身体健康之间的关联。
静息状态 fNIRS 显示，高疼痛 FOP 患者前额叶皮层慢-5 亚带（0.01-0.027 Hz）的血流动力学活动功率受到抑制，其中慢-5、前额叶皮层振荡的功率降低与疼痛程度呈显著负相关。更高的临床疼痛强度也与更高程度的抑郁症状相关。
我们的研究结果不仅表明 FOP 中前额叶皮层功能与临床疼痛之间存在稳健的耦合，而且为利用 fNIRS 客观监测 FOP 和其他肌肉骨骼疾病中的中枢疼痛机制奠定了基础。
