Garrett Jacob C, Wilson Sierra, Jessup Alexander, Brandel Michael G, Nerison Caleb S, Raslan Ahmed M, Ben-Haim Sharona, Halgren Eric
Neurosciences Graduate Program, University of California, San Diego, La Jolla, California, USA.
Scintillion Institute, San Diego, California, USA.
medRxiv. 2025 Mar 28:2025.03.03.25323046. doi: 10.1101/2025.03.03.25323046.
The nature of the neurophysiological effects of opioids, especially those responsible for their analgesic properties, are unknown, hindering efforts to develop non-addictive alternatives. Fentanyl and hydromorphone were administered to patients experiencing semi-chronic, clinically-relevant pain after surgical implantation of electrodes for the localization of seizure onset. Opioids suppressed beta oscillations in lateral amygdala, ventral and dorsolateral prefrontal cortices, and increased beta in medial amygdala and hippocampus. Opioids also suppressed high gamma oscillations in insula and lateral amygdala, and increased high gamma in cingulate cortex and hippocampus. The amplitude of these beta effects in the ventral prefrontal cortex, medial amygdala and hippocampus, and of gamma effects in the insula, were positively correlated with the magnitude of pain relief in response to a constant dose. These findings identify electrophysiological events in a network of limbic structures that may participate in opioidergic pain relief through nociceptive gating and a decreased concerned fixation on pain, providing insights into the neural basis of pain relief and suggesting possible biomarkers for developing non-addictive opioid alternatives.
阿片类药物的神经生理效应，尤其是那些与其镇痛特性相关的效应的本质尚不清楚，这阻碍了开发无成瘾性替代药物的努力。在为癫痫发作起始部位定位而进行电极手术植入后，向患有半慢性、临床相关疼痛的患者施用了芬太尼和氢吗啡酮。阿片类药物抑制了外侧杏仁核、腹侧和背外侧前额叶皮质的β振荡，并增加了内侧杏仁核和海马体中的β振荡。阿片类药物还抑制了岛叶和外侧杏仁核中的高γ振荡，并增加了扣带回皮质和海马体中的高γ振荡。腹侧前额叶皮质、内侧杏仁核和海马体中这些β效应的幅度，以及岛叶中γ效应的幅度，与恒定剂量下的疼痛缓解程度呈正相关。这些发现确定了边缘结构网络中的电生理事件，这些事件可能通过伤害性刺激闸门控制和减少对疼痛的关注参与阿片类药物介导的疼痛缓解，为疼痛缓解的神经基础提供了见解，并为开发无成瘾性阿片类替代药物提示了可能的生物标志物。
