William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, EC1M 6BQ London, United Kingdom.
Institute of Biomedical and Oral Research, Hebrew University, 9112102 Jerusalem, Israel.
Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2211631120. doi: 10.1073/pnas.2211631120. Epub 2023 Apr 18.
Fibromyalgia is a debilitating widespread chronic pain syndrome that occurs in 2 to 4% of the population. The prevailing view that fibromyalgia results from central nervous system dysfunction has recently been challenged with data showing changes in peripheral nervous system activity. Using a mouse model of chronic widespread pain through hyperalgesic priming of muscle, we show that neutrophils invade sensory ganglia and confer mechanical hypersensitivity on recipient mice, while adoptive transfer of immunoglobulin, serum, lymphocytes, or monocytes has no effect on pain behavior. Neutrophil depletion abolishes the establishment of chronic widespread pain in mice. Neutrophils from patients with fibromyalgia also confer pain on mice. A link between neutrophil-derived mediators and peripheral nerve sensitization is already established. Our observations suggest approaches for targeting fibromyalgia pain via mechanisms that cause altered neutrophil activity and interactions with sensory neurons.
纤维肌痛是一种使人虚弱的广泛慢性疼痛综合征，其在人群中的发生率为 2%至 4%。最近，有数据显示外周神经系统活动的变化，这对纤维肌痛是由中枢神经系统功能障碍引起的这一主流观点提出了挑战。通过肌肉痛觉过敏引发的慢性广泛性疼痛的小鼠模型，我们发现中性粒细胞会侵入感觉神经节，并使接受的小鼠产生机械性痛觉过敏，而免疫球蛋白、血清、淋巴细胞或单核细胞的过继转移对痛觉行为没有影响。中性粒细胞耗竭可阻止小鼠建立慢性广泛性疼痛。纤维肌痛患者的中性粒细胞也会使小鼠产生疼痛。中性粒细胞衍生介质与外周神经敏化之间的联系已经建立。我们的观察结果表明，通过导致中性粒细胞活性改变和与感觉神经元相互作用的机制，为治疗纤维肌痛疼痛提供了方法。
