Activation of the Notch signaling pathway in the anterior cingulate cortex is involved in the pathological process of neuropathic pain
| Autor: | Zhiyi Tu, Pei Chen, Li Li, Haifeng Duan, Ping Chen, Feng-Yan Shen, Zhi-Ru Wang, Weimin Liang, Ying-Wei Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Notch signaling pathway HES5 Neurotransmission Neuropathic pain Gyrus Cinguli Synaptic Transmission Anterior cingulate cortex Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine 030202 anesthesiology medicine Animals HES1 business.industry Chronic pain Long-term potentiation Nerve injury Central sensitization medicine.disease Rats Anesthesiology and Pain Medicine Neurology Neuralgia Neurology (clinical) medicine.symptom business Neuroscience 030217 neurology & neurosurgery Research Paper Signal Transduction |
| Zdroj: | Pain |
| ISSN: | 1872-6623 0304-3959 |
| Popis: | This study reveals interfering Notch signaling pathway of anterior cingulate cortex in early phase prevents neuropathic pain progress by inhibiting the potentiation of synaptic transmission. Plastic changes in the anterior cingulate cortex (ACC) are critical in pain hypersensitivity caused by peripheral nerves injury. The Notch signaling pathway has been shown to regulate synaptic differentiation and transmission. Therefore, this study was to investigate the function of the Notch signaling pathway in the ACC during nociceptive transmission induced by neuropathic pain. We adopted Western blotting, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) microinjections, RNA interference targeting Notch1, Hairy and enhancer of split (Hes) 1 or Hes5, electrophysiological recordings, and behavioral tests to verify the link between Notch signaling in ACC and neuropathic pain with adult male Sprague-Dawley rats. Levels of the Notch intracellular domain were increased in ACC on day 7 after chronic constriction injury surgery or spared nerve injury. Meanwhile, the mRNA level of the downstream effector of Notch signaling Hes1 was increased, whereas the level of Hes5 mRNA did not change. Microinjection of DAPT, a γ-secretase (a key enzyme involved in Notch pathway) inhibitor, into ACC significantly reversed neuropathic pain behaviors. Intra-ACC injection of short hairpin RNA-Notch reduced Notch intracellular domain expression and decreased the potentiation of synaptic transmission in the ACC. Moreover, pain perceptions were also alleviated in rats subjected to chronic constriction injury or spared nerve injury. This process was mainly mediated by the downstream effector Hes1, but not Hes5. Based on these results, the activation of the Notch/Hes1 signaling pathway in the ACC participates in the development of neuropathic pain, indicating that the Notch pathway may be a new therapeutic target for treating chronic pain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|