Angelini Pharma S.p.A., Viale Amelia, 70, 00181, Rome, Italy.
Transpharmation Ireland Ltd., Trinity College Dublin-Institute of Neuroscience (TCIN), Lloyd Institute, Trinity College, Dublin 2, Ireland.
Sci Rep. 2021 May 12;11(1):10139. doi: 10.1038/s41598-021-89629-y.
Post-operative cognitive dysfunction (POCD) is a debilitating clinical phenomenon in elderly patients. Management of pain in elderly is complicated because analgesic opiates elicit major side effects. In contrast, paracetamol (acetaminophen) has shown analgesic efficacy, no impact on cognition, and its side effects are well tolerated. We investigated the efficacy of paracetamol, compared to the opioid analgesic buprenorphine, in a model of POCD by investigating cognitive decline, allodynia, peripheral and hippocampal cytokines levels, and hippocampal microtubule dynamics as a key modulator of synaptic plasticity. A POCD model was developed in middle-aged (MA) rats by inducing a tibia fracture via orthopaedic surgery. Control MA rats did not undergo any surgery and only received isoflurane anaesthesia. We demonstrated that cognitive decline and increased allodynia following surgery was prevented in paracetamol-treated animals, but not in animals which were exposed to anesthesia alone or underwent the surgery and received buprenorphine. Behavioral alterations were associated with different peripheral cytokine changes between buprenorphine and paracetamol treated animals. Buprenorphine showed no central effects, while paracetamol showed modulatory effects on hippocampal cytokines and markers of microtubule dynamics which were suggestive of neuroprotection. Our data provide the first experimental evidence corroborating the use of paracetamol as first-choice analgesic in POCD.
术后认知功能障碍（POCD）是老年患者一种使人虚弱的临床现象。老年患者的疼痛管理较为复杂，因为阿片类镇痛药会引起主要的副作用。相比之下，对乙酰氨基酚（扑热息痛）已显示出镇痛效果，对认知没有影响，且其副作用可耐受良好。我们通过研究认知衰退、痛觉过敏、外周和海马细胞因子水平以及海马微管动力学（作为突触可塑性的关键调节剂），调查了扑热息痛与阿片类镇痛药丁丙诺啡在 POCD 模型中的疗效。通过骨科手术诱导胫骨骨折，建立中年（MA）大鼠 POCD 模型。未接受任何手术的对照 MA 大鼠仅接受异氟烷麻醉。我们证明，扑热息痛治疗可预防手术后认知衰退和痛觉过敏，但单独接受麻醉或接受手术并接受丁丙诺啡的大鼠则无法预防。行为改变与丁丙诺啡和扑热息痛治疗动物之间不同的外周细胞因子变化有关。丁丙诺啡无中枢作用，而扑热息痛对海马细胞因子和微管动力学标志物有调节作用，提示有神经保护作用。我们的数据提供了首个实验证据，支持将扑热息痛作为 POCD 的首选镇痛剂。
