Hammers Alexander, Asselin Marie-Claude, Hinz Rainer, Kitchen Ian, Brooks David J, Duncan John S, Koepp Matthias J
MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, Hammersmith Hospital, London, UK.
Brain. 2007 Apr;130(Pt 4):1009-16. doi: 10.1093/brain/awm012. Epub 2007 Feb 14.
Animal and limited human data suggest an important anticonvulsant role for opioid peptides and their receptors. We aimed to provide direct human in vivo evidence for changes in opioid receptor availability following spontaneous seizures. We scanned nine patients within hours of spontaneous temporal lobe seizures and compared their postictal binding of the non-subtype selective opioid receptor PET radioligand [11C]diprenorphine (DPN), quantified as a volume-of-distribution (VD), with interictal binding and with binding changes in 14 healthy controls, controlling for a range of behavioural variables associated with opioid action. A regionally specific increase of opioid receptor availability was evident in the temporal pole and fusiform gyrus ipsilateral to the seizure focus following seizures (Z 5.01, P < 0.001, 16 432 mm3). Within this region, there was a negative correlation between VD and log10 time since last seizure (r = -0.53, P < 0.03), compatible with an early increase and gradual return to baseline. [11C]DPN VD did not undergo systematic changes between time points in controls. This study provides direct human in vivo evidence for changes in opioid receptor availability over a time course of hours following spontaneous seizures, emphasizing an important role of the opioid system in seizure control.
动物实验和有限的人体数据表明，阿片肽及其受体具有重要的抗惊厥作用。我们旨在为自发性癫痫发作后阿片受体可用性的变化提供直接的人体体内证据。我们在9例患者发生自发性颞叶癫痫发作后的数小时内对其进行了扫描，并将他们发作后非亚型选择性阿片受体PET放射性配体[11C]二丙诺啡（DPN）的结合情况（以分布容积（VD）量化）与发作间期结合情况以及14名健康对照者的结合变化进行了比较，同时控制了一系列与阿片作用相关的行为变量。癫痫发作后，在癫痫病灶同侧的颞极和梭状回中，阿片受体可用性出现了区域特异性增加（Z = 5.01，P < 0.001，16 432 mm3）。在该区域内，VD与距上次发作的log10时间呈负相关（r = -0.5），P < 0.03），这与早期增加并逐渐恢复到基线水平相符。在对照者中，[11C]DPN的VD在各时间点之间未发生系统性变化。本研究为自发性癫痫发作后数小时内阿片受体可用性的变化提供了直接的人体体内证据，强调了阿片系统在癫痫控制中的重要作用。
