Activation of the dorsal, but not the ventral, hippocampus relieves neuropathic pain in rodents.
Activation of the dorsal, but not the ventral, hippocampus relieves neuropathic pain in rodents.
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激活背侧海马体而非腹侧海马体可缓解啮齿类动物的神经性疼痛
DOI：
10.1097/j.pain.0000000000002279
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发表时间：
2021-12-01
期刊：
影响因子：
7.4
通讯作者：
Apkarian AV
中科院分区：
文献类型：
--
作者：
Wei X;Centeno MV;Ren W;Borruto AM;Procissi D;Xu T;Jabakhanji R;Mao Z;Kim H;Li Y;Yang Y;Gutruf P;Rogers JA;Surmeier DJ;Radulovic J;Liu X;Martina M;Apkarian AV
补充数字内容在文本中可用。药理学、光遗传学和化学遗传学调节背侧海马而不是腹侧海马的神经元兴奋性在神经病理性疼痛的啮齿动物模型中诱导镇痛。越来越多的证据表明慢性疼痛表型下的海马损伤。然而，目前尚不清楚神经病理行为是否与海马回路功能障碍有关。在这里，我们通过药理学、光遗传学和化学遗传学技术增强海马活性，以确定海马对神经病理性疼痛行为的影响。我们发现，兴奋的背侧（DH），而不是腹侧（VH）海马诱导镇痛在2啮齿动物模型的神经性疼痛（SNI和SNL）和大鼠和小鼠。对DH神经元的光遗传学和药理学操作表明，DH诱导的镇痛作用是由N-甲基-D-天冬氨酸和μ-阿片受体介导的。除了镇痛之外，SNI小鼠中DH的光遗传学刺激还导致对DH被激活的腔室的实时条件性位置偏好增强，这一发现与疼痛缓解一致。在VH中进行类似操作无效。使用化学功能磁共振成像（fMRI），其中清醒的静息状态fMRI结合病毒载体介导的化学发生激活（PSAM/PSEM 89）的DH神经元，我们证明了DH和丘脑和体感区域之间的功能连接的变化，跟踪触觉异常性疼痛的缓解程度。此外，我们还研究了人类海马的功能连接，并观察了亚急性和慢性背痛之间海马前部和后部分区的差异重组。总而言之，这些结果意味着在慢性神经性疼痛过程中DH回路的下调会导致疼痛相关行为。相反，DH的激活通过影响DH功能连接的局部兴奋性和阿片样物质能机制逆转疼痛相关行为。因此，这项研究显示了一个新的因果关系的作用，DH，而不是VH在控制神经性疼痛相关的行为。
Supplemental Digital Content is Available in the Text. Pharmacological, optogenetic, and chemogenetic modulation of neuronal excitability of the dorsal, but not the ventral, hippocampus induces analgesia in rodent models of neuropathic pain. Accumulating evidence suggests hippocampal impairment under the chronic pain phenotype. However, it is unknown whether neuropathic behaviors are related to dysfunction of the hippocampal circuitry. Here, we enhanced hippocampal activity by pharmacological, optogenetic, and chemogenetic techniques to determine hippocampal influence on neuropathic pain behaviors. We found that excitation of the dorsal (DH), but not the ventral (VH) hippocampus induces analgesia in 2 rodent models of neuropathic pain (SNI and SNL) and in rats and mice. Optogenetic and pharmacological manipulations of DH neurons demonstrated that DH-induced analgesia was mediated by N-Methyl-D-aspartate and μ-opioid receptors. In addition to analgesia, optogenetic stimulation of the DH in SNI mice also resulted in enhanced real-time conditioned place preference for the chamber where the DH was activated, a finding consistent with pain relief. Similar manipulations in the VH were ineffective. Using chemo-functional magnetic resonance imaging (fMRI), where awake resting-state fMRI was combined with viral vector-mediated chemogenetic activation (PSAM/PSEM89s) of DH neurons, we demonstrated changes of functional connectivity between the DH and thalamus and somatosensory regions that tracked the extent of relief from tactile allodynia. Moreover, we examined hippocampal functional connectivity in humans and observe differential reorganization of its anterior and posterior subdivisions between subacute and chronic back pain. Altogether, these results imply that downregulation of the DH circuitry during chronic neuropathic pain aggravates pain-related behaviors. Conversely, activation of the DH reverses pain-related behaviors through local excitatory and opioidergic mechanisms affecting DH functional connectivity. Thus, this study exhibits a novel causal role for the DH but not the VH in controlling neuropathic pain–related behaviors.
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影响因子：
2.9
作者：
Gurtskaia G;Tsiklauri N;Nozadze I;Nebieridze M;Tsagareli MG
通讯作者：
Tsagareli MG
我们能否调和关于海马功能的陈述性记忆和空间导航观点？
影响因子：
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作者：
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