Objective Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee OA and is often refractory to conventional interventions. Tapentadol, as an opioid receptor agonist and noradrenaline reuptake inhibitor, has been proposed as a potentially effective symptomatic treatment for pain-sensitized OA patients. We empirically tested whether tapentadol could attenuate brain response to painful stimulation on the tender knee using functional MRI. Methods Painful pressure stimulation was applied to the articular interline and the tibial surface, a commonly sensitized site surrounding the joint. Thirty patients completed the crossover trial designed to compare prolonged release tapentadol and placebo effects administered over 14 days. Results We found no effects in the direction of the prediction. Instead, patients administered with tapentadol showed stronger activation in response to pressure on the tender site in the right prefrontal cortex and somatosensory cortices. The somatosensory effect was compatible with the spread of neural activation around the knee cortical representation. Consistent with the functional MRI findings, the patients showed higher clinical ratings of pain sensitization under tapentadol and a significant positive association was identified between the number of tapentadol tablets and the evoked subjective pain. Conclusion The tapentadol effect paradoxically involved both the spread of the somatosensory cortex response and a stronger activation in prefrontal areas with a recognized role in the appraisal of pain sensations. Further studies are warranted to explore how OA patients may benefit from powerful analgesic drugs without the associated risks of prolonged use. Trial registration EudraCT, https://eudract.ema.europa.eu, 2016–005082-31.

中文翻译：

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他喷他多对致敏性膝骨关节炎患者大脑对疼痛的反应的影响

目的 疼痛敏化，表现为膝关节压痛和解剖学上的痛觉过敏，在膝关节 OA 患者中尤为常见，并且通常对常规干预无效。他喷他多作为一种阿片受体激动剂和去甲肾上腺素再摄取抑制剂，已被提议作为疼痛敏感型 OA 患者潜在有效的对症治疗。我们经验性地测试了他喷他多是否可以使用功能性 MRI 减弱大脑对柔软膝关节疼痛刺激的反应。方法 对关节间线和胫骨表面施加疼痛的压力刺激，胫骨表面是关节周围常见的敏感部位。30 名患者完成了交叉试验，该试验旨在比较 14 天内给药的缓释他喷他多和安慰剂的效果。结果 我们发现预测方向没有影响。相反，服用他喷他多的患者对右侧前额叶皮层和体感皮层压痛部位的压力表现出更强的激活。体感效应与膝关节皮层表现周围的神经激活传播相一致。与功能性 MRI 结果一致，患者在他喷他多下的疼痛敏感性临床评分较高，并且在他喷他多片剂的数量与诱发的主观疼痛之间发现了显着的正相关。结论 他喷他多的作用自相矛盾地涉及体感皮层反应的传播和前额叶区域更强的激活，在疼痛感觉的评估中具有公认的作用。需要进一步的研究来探索 OA 患者如何从强效镇痛药物中受益，而不会带来长期使用的相关风险。试用注册 EudraCT，https://eudract.ema.europa.eu，2016-005082-31。