Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia.
Neutrophils infiltrate sensory ganglia and mediate chronic widespread pain in fibromyalgia.
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DOI：
10.1073/pnas.2211631120
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发表时间：
2023-04-25
影响因子：
11.1
通讯作者：
Sikandar, Shafaq
中科院分区：
文献类型：
--
作者：
Caxaria, Sara;Bharde, Sabah;Fuller, Alice M.;Evans, Romy;Thomas, Bethan;Celik, Petek;Dell'Accio, Francesco;Yona, Simon;Gilroy, Derek;Voisin, Mathieu-Benoit;Wood, John N.;Sikandar, Shafaq
我们在小鼠中使用反翻译方法来证明中性粒细胞在纤维肌痛中的前感觉作用。慢性广发疼痛小鼠或纤维肌痛患者的中性粒细胞过继性转移可使受体naïve小鼠产生机械性疼痛，使脊髓神经元的诱发动作电位发射敏感，并使中性粒细胞蛋白细胞表面表达发生表型变化，导致中性粒细胞浸润到背根神经节。这些数据为多形核粒细胞介导的纤维肌痛慢性广泛性疼痛的免疫学基础提供了框架。纤维肌痛是一种使人衰弱的广泛慢性疼痛综合征，发生在人口的2%至4%。纤维肌痛由中枢神经系统功能障碍引起的流行观点最近受到了周围神经系统活动变化的数据的挑战。通过肌肉痛觉引发的慢性广泛性疼痛小鼠模型，我们发现中性粒细胞侵入感觉神经节并使受体小鼠产生机械过敏，而免疫球蛋白、血清、淋巴细胞或单核细胞的过继性转移对疼痛行为没有影响。中性粒细胞耗竭消除小鼠慢性广泛性疼痛的建立。纤维肌痛患者体内的中性粒细胞也会给小鼠带来疼痛。中性粒细胞衍生介质和周围神经致敏之间的联系已经建立。我们的观察结果建议通过改变中性粒细胞活动和与感觉神经元相互作用的机制来靶向纤维肌痛疼痛。
We used a back-translational approach in mice to demonstrate the pronociceptive role of neutrophils in fibromyalgia. Adoptive transfer of neutrophils from mice with chronic widespread pain or from patients with fibromyalgia can confer mechanical pain to recipient naïve mice, sensitize evoked action potential firing of spinal cord neurons, and produce phenotypic changes in cell surface expression of neutrophil proteins that cause infiltration of neutrophils into dorsal root ganglia. These data provide the framework for an immunological basis of chronic widespread pain in fibromyalgia mediated by polymorphonuclear granulocytes. 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.
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影响因子：
5.6
作者：
Kiguchi N;Kobayashi D;Saika F;Matsuzaki S;Kishioka S
通讯作者：
Kishioka S
影响因子：
7.4
作者：
Bennett, G;al-Rashed, S;Brain, SD
通讯作者：
Brain, SD
影响因子：
17.1
作者：
Dawes JM;Calvo M;Perkins JR;Paterson KJ;Kiesewetter H;Hobbs C;Kaan TK;Orengo C;Bennett DL;McMahon SB
通讯作者：
McMahon SB
影响因子：
5.5
作者：
Cunha, Thiago M.;Verri, Waldiceu A., Jr.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.
影响因子：
3.6
作者：
Affaitati, Giannapia;Costantini, Raffaele;Giamberardino, Maria Adele
通讯作者：
Giamberardino, Maria Adele