Crock Lara W, Baldridge Megan T
Department of Anesthesiology and Pain Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Division of Infectious Diseases, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
Neurobiol Pain. 2020 Nov 25;8:100054. doi: 10.1016/j.ynpai.2020.100054. eCollection 2020 Aug-Dec.
Complex regional pain syndrome (CRPS) is a debilitating neuroinflammatory condition of unknown etiology. Symptoms include excruciating pain and trophic changes in the limbs as defined by the Budapest criteria. The severity and functional recovery of CRPS, unlike most pain conditions, is quantifiable using a variation of the Budapest criteria known as the CRPS severity score. Like many chronic pain conditions, CRPS is difficult to treat once pain has been present for more than 12 months. However, previous work has demonstrated that a subset of patients with new-onset CRPS (~50%) improve if treated within one year, while the rest have minimal to no symptom improvement. Unfortunately, this leads to permanent disability and often requires invasive and costly treatments such as spinal cord stimulation or long-term opioid therapy. Because the etiology is unknown, treatment is multimodal, and often supportive. Biomarkers that predict severity or resolution of symptoms would significantly change treatment but have not yet been identified. Interestingly, there are case reports of remission or resolution of CRPS symptoms with the use of antibiotics known to affect the gut flora. Mouse studies have demonstrated that modulation of the gut microbiome is anti-nociceptive in visceral, inflammatory and neuropathic pain models. We hypothesize that the variable clinical potential for recovery and response to therapy in CRPS may be secondary to or reflected in changes in the gut microbiota. We suggest that the microbiota may mediate or reflect clinical status via the metabolome, activation of the immune system and/or microglial activation. We hypothesize that the gut microbiome is a potential mediator in development and persistence of CRPS symptoms and propose that the clinical condition of CRPS could provide a unique opportunity to identify biomarkers of the microbiota and potential therapies to prevent pain chronification.
复杂性区域疼痛综合征（CRPS）是一种病因不明的使人衰弱的神经炎症性病症。症状包括布达佩斯标准所定义的四肢剧痛和营养改变。与大多数疼痛病症不同，CRPS的严重程度和功能恢复情况可使用一种名为CRPS严重程度评分的布达佩斯标准变体进行量化。和许多慢性疼痛病症一样，一旦疼痛持续超过12个月，CRPS就很难治疗。然而，先前的研究表明，一部分新发CRPS患者（约50%）如果在一年内接受治疗会有所改善，而其余患者症状改善甚微或没有改善。不幸的是，这会导致永久性残疾，并且常常需要脊髓刺激或长期阿片类药物治疗等侵入性且昂贵的治疗方法。由于病因不明，治疗是多模式的，且通常是支持性的。能够预测症状严重程度或缓解情况的生物标志物会显著改变治疗方式，但目前尚未确定。有趣的是，有使用已知会影响肠道菌群的抗生素后CRPS症状缓解或消退的病例报告。小鼠研究表明，在内脏、炎症和神经性疼痛模型中，调节肠道微生物群具有抗伤害感受作用。我们推测，CRPS恢复和对治疗反应的临床潜力差异可能继发于肠道微生物群的变化或在其中得到体现。我们认为，微生物群可能通过代谢组、免疫系统激活和/或小胶质细胞激活来介导或反映临床状态。我们推测肠道微生物群是CRPS症状发生和持续的潜在介导因素，并提出CRPS的临床病症可能为识别微生物群生物标志物和预防疼痛慢性化的潜在疗法提供独特机会。
