Activation of the dorsal, but not the ventral, hippocampus relieves neuropathic pain in rodents
| Autor: | Haram Kim, Zuchao Mao, Marco Martina, Yiyuan Yang, Xuhong Wei, Philipp Gutruf, Jelena Radulovic, Apkar Vania Apkarian, Daniele Procissi, Yajing Li, Maria Virginia Centeno, Wenjie Ren, D. James Surmeier, Xian-Guo Liu, Anna Maria Borruto, Rami Jabakhanji, John A. Rogers, Ting Xu |
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| Rok vydání: | 2021 |
| Předmět: |
SNi
Thalamus Hippocampus Rodentia Optogenetics Hippocampal formation Neuropathic pain Somatosensory system Mice GABA 03 medical and health sciences 0302 clinical medicine 030202 anesthesiology Animals Medicine Rats Wistar Neurons business.industry Wireless optogenetics fMRI Chronic pain medicine.disease Rats Opioids Anesthesiology and Pain Medicine nervous system Neurology Neuralgia Neurology (clinical) Glutamate Analgesia business Neuroscience 030217 neurology & neurosurgery Research Paper |
| Zdroj: | Pain |
| ISSN: | 1872-6623 0304-3959 |
| DOI: | 10.1097/j.pain.0000000000002279 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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