Resident Macrophages in Muscle Contribute to Development of Hyperalgesia in a Mouse Model of Noninflammatory Muscle Pain.
Resident Macrophages in Muscle Contribute to Development of Hyperalgesia in a Mouse Model of Noninflammatory Muscle Pain.
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DOI：
10.1016/j.jpain.2016.06.010
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发表时间：
2016-10
期刊：
影响因子：
4
通讯作者：
Sluka, Kathleen A.
中科院分区：
文献类型：
--
作者：
Gong, Wei-Yi;Abdelhamid, Ramy E.;Carvalho, Carolina S.;Sluka, Kathleen A.
巨噬细胞在体内的先天免疫中起作用，位于肌肉组织中，并且可以释放致敏局部伤害感受器的炎性细胞因子。在这里，我们研究了驻留巨噬细胞在腓肠肌中间隔5天注射2次pH 4.0诱导的非炎性肌肉疼痛模型中的作用。我们证明，注射2 pH 4.0注射到腓肠肌增加了局部肌肉巨噬细胞的数量，并消耗肌肉巨噬细胞与氯膦酸脂质体酸注射前衰减该模型产生的痛觉过敏。为了进一步研究局部巨噬细胞对这种痛觉过敏的贡献，我们给小鼠肌内注射C34，一种TLR 4受体拮抗剂。当在第一次pH 4.0注射之前给予时，C34减弱了模型产生的肌肉和触觉痛觉过敏。然而，当在第二次注射之前给予C34时，对痛觉过敏的发展没有影响。然后，为了测试局部巨噬细胞的激活是否使伤害感受器对正常非伤害感受性刺激敏感，我们用免疫细胞激活剂脂多糖（LPS）或炎性细胞因子白细胞介素-6（IL-6）代替第一次或第二次酸注射。注射LPS或IL-6而不是第一次或第二次pH 4.0注射导致缩爪反应的剂量依赖性增加和肌肉缩爪阈值的降低。最高剂量的LPS和IL-6导致双侧痛觉过敏的发展。目前的研究表明，肌肉中的常驻巨噬细胞是慢性肌肉疼痛发展的关键。
Macrophages play a role in innate immunity within the body, are located in muscle tissue, and can release inflammatory cytokines that sensitize local nociceptors. Here we investigate the role of resident macrophages in the non-inflammatory muscle pain model induced by 2 pH 4.0 injections 5 days apart in the gastrocnemius muscle. We demonstrate that injecting 2 pH 4.0 injections into the gastrocnemius muscle increased the number of local muscle macrophages, and depleting muscle macrophages with clodronate liposomes prior to acid injections attenuated the hyperalgesia produced by this model. To further examine the contribution of local macrophages to this hyperalgesia, we injected mice intramuscularly with C34, a TLR4 receptor antagonist. When given before the first pH 4.0 injection, C34 attenuated the muscle and tactile hyperalgesia produced by the model. However, when given before the second injection C34 had no effect on the development of hyperalgesia. Then to test whether activation of local macrophages sensitizes nociceptors to normally non-nociceptive stimuli we replaced either the first or second acid injection with the immune cell activator lipopolysaccharide (LPS), or the inflammatory cytokine interleukin-6 (IL-6). Injecting LPS or IL-6 instead of the either the first or second pH 4.0 injection resulted in a dose-dependent increase in paw withdrawal responses and decrease in muscle withdrawal thresholds. The highest doses of LPS and IL-6 resulted in development of hyperalgesia bilaterally. The present study shows that resident macrophages in muscle are key to development of chronic muscle pain.
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影响因子：
7.4
作者：
Leung A;Gregory NS;Allen LH;Sluka KA
通讯作者：
Sluka KA
影响因子：
5.1
作者：
Gregory, Nicholas S.;Brito, Renan G.;Oliveira Fusaro, Maria Claudia G.;Sluka, Kathleen A.
通讯作者：
Sluka, Kathleen A.
DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
3.3
作者：
Helley, M. P.;Abate, W.;Thompson, S. W. N.
通讯作者：
Thompson, S. W. N.