Anesthesiology Service, Veterans Administration Palo Alto Health Care System, Palo Alto, California, and Department of Anesthesia, Stanford University, Palo Alto, California, USA.
Anesthesiology. 2012 Sep;117(3):602-12. doi: 10.1097/ALN.0b013e3182655f9f.
Neutrophils are one of the predominant immune cells initially migrating to surgical wound edges. They produce mediators both associated with supporting (interleukin [IL]-1β, C5a) and reducing (opioid peptides) pain. Studies demonstrate neutrophil depletion/blockade reduces nociceptive sensitization after nerve injury and carrageenan administration, but enhance sensitization in complete Freund's adjuvant inflammation. This research identifies the contribution of infiltrating neutrophils to incisional pain and inflammation.
Antibody-mediated Gr1 neutrophil depletion preceded hind paw incisions. Sensitization to mechanical and thermal stimuli, effects on edema and local levels of IL-1β and C5a were measured. Local effects of C5a or IL-1 receptor antagonists PMX-53 and anakinra on sensitization after neutrophil depletion were examined. Groups of 4-8 mice were used.
Anti-Gr1 antibody depleted more than 90% of circulating and infiltrating skin neutrophils after incision. Neutrophil depletion did not change magnitude or duration of mechanical hypersensitivity in incised mice. However, paw edema was significantly reduced and heat hypersensitivity was slightly increased in depleted animals. In depleted animals IL-1β levels were half of controls 24 h after incision, whereas C5a levels were increased in both. Prominent IL-1β immunohistochemical staining of epidermis was seen in both groups. PMX-53 and anakinra reduced incisional mechanical and heat nociceptive sensitization to the same extent, regardless of neutrophil depletion.
Neutrophil-derived IL-1β and C5a do not appear to contribute critically to peri-incisional nociceptive signaling. Other sources of mediators, such as epidermal cells, may need to be considered. Controlling inflammatory activation of resident cells in epidermis/deeper structures may show therapeutic efficacy in reducing pain from surgical incisions.
中性粒细胞是最初迁移到手术伤口边缘的主要免疫细胞之一。它们产生与支持（白细胞介素[IL]-1β、C5a）和减少（阿片肽）疼痛相关的介质。研究表明，中性粒细胞耗竭/阻断减少神经损伤和角叉菜胶给药后的伤害感受敏化，但在完全弗氏佐剂炎症中增强敏化。这项研究确定了浸润中性粒细胞对切口疼痛和炎症的贡献。
抗 Gr1 中性粒细胞耗竭抗体在前爪切口前给予。测量机械和热刺激的敏化作用、对水肿和局部 IL-1β和 C5a 水平的影响。研究了 C5a 或 IL-1 受体拮抗剂 PMX-53 和 anakinra 在中性粒细胞耗竭后对敏化作用的局部影响。每组使用 4-8 只小鼠。
抗 Gr1 抗体在切口后耗尽了超过 90%的循环和浸润皮肤中性粒细胞。中性粒细胞耗竭不会改变切口小鼠机械性超敏反应的幅度或持续时间。然而，耗竭动物的爪水肿明显减少，热敏化略有增加。在耗竭动物中，IL-1β水平在切口后 24 小时是对照组的一半，而 C5a 水平在两组中均增加。两组均可见表皮 IL-1β免疫组织化学染色明显。PMX-53 和 anakinra 无论中性粒细胞耗竭与否，均能同等程度地减少切口机械和热伤害感受敏化。
中性粒细胞衍生的 IL-1β 和 C5a 似乎对围手术切口疼痛信号传递没有重要作用。可能需要考虑其他来源的介质，如表皮细胞。控制表皮/更深层结构中常驻细胞的炎症激活可能会显示出减少手术切口疼痛的治疗效果。
