Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway.
Pain Research Group, Department of Anesthesiology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.
Pain. 2018 Jun;159(6):1064-1073. doi: 10.1097/j.pain.0000000000001188.
P2X7 is a nonselective cation channel activated by extracellular ATP. P2X7 activation contributes to the proinflammatory response to injury or bacterial invasion and mediates apoptosis. Recently, P2X7 function has been linked to chronic inflammatory and neuropathic pain. P2X7 may contribute to pain modulation both by effects on peripheral tissue injury underlying clinical pain states, and through alterations in central nervous system processing, as suggested by animal models. To further test its role in pain sensitivity, we examined whether variation within the P2RX7 gene, which encodes the P2X7 receptor, was associated with experimentally induced pain in human patients. Experimental pain was assessed in Tromsø 6, a longitudinal and cross-sectional population-based study (N = 3016), and the BrePainGen cohort, consisting of patients who underwent breast cancer surgery (N = 831). For both cohorts, experimental pain intensity and tolerance were assessed with the cold-pressor test. In addition, multisite chronic pain was assessed in Tromsø 6 and pain intensity 1 week after surgery was assessed in BrePainGen. We tested whether the single-nucleotide polymorphism rs7958311, previously implicated in clinical pain, was associated with experimental and clinical pain phenotypes. In addition, we examined effects of single-nucleotide polymorphisms rs208294 and rs208296, for which previous results have been equivocal. Rs7958311 was associated with experimental pain intensity in the meta-analysis of both cohorts. Significant associations were also found for multisite pain and postoperative pain. Our results strengthen the existing evidence and suggest that P2X7 and genetic variation in the P2RX7-gene may be involved in the modulation of human pain sensitivity.
P2X7 是一种由细胞外 ATP 激活的非选择性阳离子通道。P2X7 的激活有助于对损伤或细菌入侵的促炎反应，并介导细胞凋亡。最近，P2X7 的功能与慢性炎症和神经性疼痛有关。P2X7 可能通过对临床疼痛状态下的外周组织损伤的影响以及通过对中枢神经系统处理的改变来调节疼痛，这一点被动物模型所证实。为了进一步测试其在疼痛敏感性中的作用，我们研究了编码 P2X7 受体的 P2RX7 基因内的变异是否与人类患者的实验性疼痛有关。在特罗姆瑟 6 号纵向和横断面人群基础研究（N=3016）和 BrePainGen 队列中评估了实验性疼痛，后者由接受乳腺癌手术的患者组成（N=831）。对于两个队列，均使用冷加压试验评估了实验性疼痛强度和耐受力。此外，在特罗姆瑟 6 号评估了多部位慢性疼痛，在 BrePainGen 评估了手术后 1 周的疼痛强度。我们测试了先前与临床疼痛有关的单核苷酸多态性 rs7958311 是否与实验和临床疼痛表型有关。此外，我们还研究了单核苷酸多态性 rs208294 和 rs208296 的影响，先前的结果存在争议。rs7958311 与两个队列的实验性疼痛强度的荟萃分析相关。在多部位疼痛和术后疼痛方面也发现了显著相关性。我们的结果加强了现有证据，并表明 P2X7 和 P2RX7 基因中的遗传变异可能参与了人类疼痛敏感性的调节。
