Ferrari Luiz F, Wilkinson Ashley, Donaldson Gary W, Shen Jincheng, Ramirez Anna, Rey Charles, Cahoon Christian, Miner Dashiell, Okifuji Akiko, Taylor Norman E
Department of Anesthesiology, School of Medicine, University of Utah, Salt Lake City, UT, United States.
Department of Population Health Sciences, University of Utah, Salt Lake City, UT, United States.
Pain. 2025 Apr 25. doi: 10.1097/j.pain.0000000000003600.
Fibromyalgia syndrome (FMS) is clinically diagnosed using a widespread pain index and symptom severity scores. Despite this, multivariate statistical models using clinical data consistently suggest the presence of single overarching factor that can capture much of the variation across a spectrum of biomarkers for FMS, potentially aiding diagnosis. We hypothesized that a comparable single index could be developed for preclinical FMS rat models to quantitatively compare and rigorously test new candidates for improved translational potential and therapeutic screening. We used male and female reserpine-treated Sprague Dawley (SD) rats to produce the fibromyalgia analog model (FAM) index, a tool to systematically determine the robustness of potential models of FMS. Features associated with FMS were assessed by behavior tests, including widespread nociceptive sensitivity evaluated on the hind paws ("paw") and gastrocnemius muscles ("mus") using a Randall-Selitto device, and face ("VF") using von Frey filaments; depression (by the forced swim test [FST]); anxiety (using the Elevated Zero Maze [EZM]); and fatigue (using a Home Cage Monitoring system [HCM]). A multivariate statistical analysis was used to determine the FAM index and document internal and external model validity. The index equation was calculated to be F = 0.410 × rzpaw + 0.618 × rzmus + 0.429 × rzVF + 0.455 × zFST + 0.183 × RZEZM + 0.160 × rzHCM, where each z is a standardized score. Our data showed the ability of the FAM index to differentiate saline-treated SD rats as a control, "normal" group, vs either acidic saline-injected SD or Dahl S rats as models displaying fibromyalgia-like behaviors.
纤维肌痛综合征(FMS)通过广泛疼痛指数和症状严重程度评分进行临床诊断。尽管如此,使用临床数据的多变量统计模型一直表明存在一个单一的总体因素,该因素可以捕捉FMS一系列生物标志物中的大部分变异,可能有助于诊断。我们假设可以为临床前FMS大鼠模型开发一个类似的单一指数,以定量比较并严格测试具有更高转化潜力和治疗筛选价值的新候选物。我们使用经利血平处理的雄性和雌性斯普拉格-道利(SD)大鼠来生成纤维肌痛类似模型(FAM)指数,这是一种系统确定FMS潜在模型稳健性的工具。通过行为测试评估与FMS相关的特征,包括使用兰德尔-塞利托装置在后爪(“爪”)和腓肠肌(“肌肉”)上评估广泛的伤害性敏感性,以及使用冯·弗里氏细丝在面部(“VF”)评估;抑郁(通过强迫游泳试验[FST]);焦虑(使用高架零迷宫[EZM]);以及疲劳(使用笼内监测系统[HCM])。使用多变量统计分析来确定FAM指数并记录模型的内部和外部有效性。指数方程计算为F = 0.410 × rzpaw + 0.618 × rzmus + 0.429 × rzVF + 0.455 × zFST + 0.183 × RZEZM + 0.160 × rzHCM,其中每个z是一个标准化分数。我们的数据表明,FAM指数能够区分作为对照的生理盐水处理的SD大鼠“正常”组与作为表现出纤维肌痛样行为模型的酸性盐水注射的SD大鼠或达尔大鼠。