Lopes Douglas M, Denk Franziska, Chisholm Kim I, Suddason Tesha, Durrieux Camille, Thakur Matthew, Gentry Clive, McMahon Stephen B
Wolfson Centre for Age-Related Diseases, King's College London, United Kingdom.
Pain. 2017 Jul;158(7):1314-1322. doi: 10.1097/j.pain.0000000000000917.
The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. To clarify whether MC are involved in inflammatory pain states, we used a transgenic mouse line (Mctp5Cre-iDTR) in which MC could be depleted in an inducible manner by administration of diphtheria toxin. Our results show that ablation of MC in male mice did not result in any change in mechanical and thermal hypersensitivity in the CFA model of inflammatory pain. Similarly, edema and temperature triggered by CFA inflammation at the injection site remained identical in MC depleted mice compared with their littermate controls. In addition, we show that Mctp5Cre-iDTR mice display normal levels of mechanical hypersensitivity after local injection of nerve growth factor (NGF), a factor well characterised to produce peripheral sensitisation and for being upregulated upon injury and inflammation. We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.
免疫和感觉系统以其紧密的邻近性和相互作用而闻名。事实上，在多种疼痛状态下，大量不同的免疫细胞被激活并募集，在神经元致敏中发挥关键作用。在炎症性疼痛期间，肥大细胞（MC）被认为是参与这一过程的免疫细胞类型之一，但迄今为止，概述其对神经元细胞直接作用的证据仍不清楚。为了阐明MC是否参与炎症性疼痛状态，我们使用了一种转基因小鼠品系（Mctp5Cre-iDTR），通过给予白喉毒素可以以诱导方式清除MC。我们的结果表明，在炎症性疼痛的CFA模型中，雄性小鼠MC的消融并未导致机械性和热超敏反应的任何变化。同样，与同窝对照小鼠相比，MC缺失小鼠注射部位由CFA炎症引发的水肿和温度保持相同。此外，我们表明，在局部注射神经生长因子（NGF）后，Mctp5Cre-iDTR小鼠表现出正常水平的机械性超敏反应，NGF是一种已被充分表征可产生外周致敏且在损伤和炎症时上调的因子。我们还证明，体外NGF处理不会导致骨髓来源的MC中肿瘤坏死因子-α水平升高。此外，我们的qRT-PCR数据显示，MC表达的NGF受体水平可忽略不计，从而解释了对NGF缺乏反应的原因。总之，我们的数据表明，在炎症状态下，MC在外周致敏中不发挥直接作用。
