Luchting Benjamin, Heyn Jens, Woehrle Tobias, Rachinger-Adam Banafscheh, Kreth Simone, Hinske Ludwig C, Azad Shahnaz C
Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
J Neuroinflammation. 2016 May 4;13(1):100. doi: 10.1186/s12974-016-0565-z.
Despite substantial progress, pathogenesis and therapy of chronic pain are still the focus of many investigations. The ATP-gated P2X7 receptor (P2X7R) has previously been shown to play a central role in animal models of nociceptive inflammatory and neuropathic pain. Recently, we found that the adaptive immune system is involved in the pathophysiology of chronic nociceptive and neuropathic pain in humans. So far, data regarding P2X7R expression patterns on cells of the adaptive immune system of pain patients are scarce. We therefore analyzed the P2X7R expression on peripheral blood lymphocytes and monocytes, as well as serum levels of IL-1β in patients suffering from chronic nociceptive and neuropathic pain in comparison to healthy volunteers in order to identify individuals who might benefit from a P2X7R modulating therapy.
P2X7R messenger RNA (mRNA) and protein expression were determined in patients with either chronic nociceptive low back pain (CLBP) or neuropathic pain (NeP), and in healthy volunteers by quantitative real-time PCR (qPCR) and by fluorescence-assisted cell-sorting (FACS), respectively. IL-1β serum levels were measured with a multiplex cytokine assay.
Compared to healthy volunteers, P2X7R mRNA (1.6-fold, p = 0.038) and protein levels were significantly increased on monocytes (NeP: 24.6 ± 6.2, healthy volunteers: 17.0 ± 5.4; p = 0.002) and lymphocytes (NeP: 21.8 ± 6.5, healthy volunteers: 15.6 ± 5.2; p = 0.009) of patients with NeP, but not in patients with CLBP. Similarly, IL-1β serum concentrations were significantly elevated only in NeP patients (1.4-fold, p = 0.04).
A significant upregulation of P2X7R and increased IL-1β release seems to be a particular phenomenon in patients with NeP. P2X7R inhibitors may therefore represent a potential option for the treatment of this frequently intractable type of pain. German Clinical Trial Register (DRKS): Registration Trial DRKS00005954.
尽管取得了重大进展，但慢性疼痛的发病机制和治疗仍是许多研究的重点。ATP门控P2X7受体（P2X7R）此前已被证明在伤害性炎症和神经性疼痛的动物模型中起核心作用。最近，我们发现适应性免疫系统参与了人类慢性伤害性和神经性疼痛的病理生理学。到目前为止，关于疼痛患者适应性免疫系统细胞上P2X7R表达模式的数据很少。因此，我们分析了慢性伤害性和神经性疼痛患者外周血淋巴细胞和单核细胞上的P2X7R表达，以及与健康志愿者相比这些患者血清中IL-1β的水平，以确定可能从P2X7R调节治疗中受益的个体。
分别通过定量实时PCR（qPCR）和荧光辅助细胞分选（FACS）测定慢性伤害性下腰痛（CLBP）患者或神经性疼痛（NeP）患者以及健康志愿者中P2X7R信使核糖核酸（mRNA）和蛋白表达。用多重细胞因子检测法测量IL-1β血清水平。
与健康志愿者相比，NeP患者单核细胞（NeP：24.6±6.2，健康志愿者：17.0±5.4；p = 0.002）和淋巴细胞（NeP：21.8±6.5，健康志愿者：15.6±5.2；p = 0.009）上的P2X7R mRNA（1.6倍，p = 0.038）和蛋白水平显著升高，但CLBP患者未升高。同样，仅NeP患者的IL-1β血清浓度显著升高（1.4倍，p = 0.04）。
P2X7R的显著上调和IL-1β释放增加似乎是NeP患者的一种特殊现象。因此，P2X7R抑制剂可能是治疗这种常见难治性疼痛类型的一种潜在选择。德国临床试验注册中心（DRKS）：注册试验DRKS00005954。
