Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons
Neuropathic pain is a kind of chronic pain that remains difficult to treat due to its complicated underlying mechanisms. Accumulating evidence has indicated that enhanced synaptic plasticity of nociceptive interneurons in the superficial spinal dorsal horn contributes to the development of neuropath...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.640533/full |
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| author | Junlin Ouyang Xiaping Chen Shanchun Su Xiaohui Li Xueqin Xu Xinhua Yu Changbin Ke Xiaohu Zhu |
| author_facet | Junlin Ouyang Xiaping Chen Shanchun Su Xiaohui Li Xueqin Xu Xinhua Yu Changbin Ke Xiaohu Zhu |
| author_sort | Junlin Ouyang |
| collection | DOAJ |
| description | Neuropathic pain is a kind of chronic pain that remains difficult to treat due to its complicated underlying mechanisms. Accumulating evidence has indicated that enhanced synaptic plasticity of nociceptive interneurons in the superficial spinal dorsal horn contributes to the development of neuropathic pain. Neuroligin1 (NL1) is a type of excitatory postsynaptic adhesion molecule, which can mediate excitatory synaptic activity, hence promoting neuronal activation. Vglut2 is the most common marker of excitatory glutamatergic neurons. To explore the role of NL1 in excitatory neurons in nociceptive regulation, we used transgenic mice with cre recombinase expression driven by the Vglut2 promoter combined with viral vectors to knockdown the expression of NL1 in excitatory neurons in the spinal dorsal horn. We found that NL1 was upregulated in the L4–L6 spinal dorsal horn in Vglut2-cre+/– mouse subjected to spared nerve injury (SNI). Meanwhile, the expression of phosphorylated cofilin (p-cofilin) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) was also increased. Spinal microinjection of a cre-dependent NL1-targeting RNAi in Vglut2-cre+/– mouse alleviated the neuropathic pain-induced mechanical hypersensitivity and reduced the increase in p-cofilin and GluR1 caused by SNI. Taken together, NL1 in excitatory neurons regulates neuropathic pain by promoting the SNI-dependent increase in p-cofilin and GluR1 in the spinal dorsal horn. Our study provides a better understanding of the role of NL1 in excitatory neurons, which might represent a possible therapeutic target for alleviating neuropathic pain. |
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| spelling | doaj.art-f13e46b8ec1f45dcbd5939961d8c5f262022-12-21T23:05:15ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-02-011410.3389/fnmol.2021.640533640533Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory NeuronsJunlin Ouyang0Xiaping Chen1Shanchun Su2Xiaohui Li3Xueqin Xu4Xinhua Yu5Changbin Ke6Xiaohu Zhu7Department of Orthopedic Rehabilitation, Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Scientific Research, Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Anesthesiology, Institute of Anesthesiology and Pain (IAP), Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Anesthesiology, Institute of Anesthesiology and Pain (IAP), Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Anesthesiology, Institute of Anesthesiology and Pain (IAP), Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Orthopedic Rehabilitation, Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Anesthesiology, Institute of Anesthesiology and Pain (IAP), Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaDepartment of Orthopedic Rehabilitation, Taihe Hospital, Hubei University of Medicine, Shiyan, ChinaNeuropathic pain is a kind of chronic pain that remains difficult to treat due to its complicated underlying mechanisms. Accumulating evidence has indicated that enhanced synaptic plasticity of nociceptive interneurons in the superficial spinal dorsal horn contributes to the development of neuropathic pain. Neuroligin1 (NL1) is a type of excitatory postsynaptic adhesion molecule, which can mediate excitatory synaptic activity, hence promoting neuronal activation. Vglut2 is the most common marker of excitatory glutamatergic neurons. To explore the role of NL1 in excitatory neurons in nociceptive regulation, we used transgenic mice with cre recombinase expression driven by the Vglut2 promoter combined with viral vectors to knockdown the expression of NL1 in excitatory neurons in the spinal dorsal horn. We found that NL1 was upregulated in the L4–L6 spinal dorsal horn in Vglut2-cre+/– mouse subjected to spared nerve injury (SNI). Meanwhile, the expression of phosphorylated cofilin (p-cofilin) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) was also increased. Spinal microinjection of a cre-dependent NL1-targeting RNAi in Vglut2-cre+/– mouse alleviated the neuropathic pain-induced mechanical hypersensitivity and reduced the increase in p-cofilin and GluR1 caused by SNI. Taken together, NL1 in excitatory neurons regulates neuropathic pain by promoting the SNI-dependent increase in p-cofilin and GluR1 in the spinal dorsal horn. Our study provides a better understanding of the role of NL1 in excitatory neurons, which might represent a possible therapeutic target for alleviating neuropathic pain.https://www.frontiersin.org/articles/10.3389/fnmol.2021.640533/fullneuropathic painspinal cordexcitatory neuronneuroligin1cofilinGluR1 |
| spellingShingle | Junlin Ouyang Xiaping Chen Shanchun Su Xiaohui Li Xueqin Xu Xinhua Yu Changbin Ke Xiaohu Zhu Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons Frontiers in Molecular Neuroscience neuropathic pain spinal cord excitatory neuron neuroligin1 cofilin GluR1 |
| title | Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons |
| title_full | Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons |
| title_fullStr | Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons |
| title_full_unstemmed | Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons |
| title_short | Neuroligin1 Contributes to Neuropathic Pain by Promoting Phosphorylation of Cofilin in Excitatory Neurons |
| title_sort | neuroligin1 contributes to neuropathic pain by promoting phosphorylation of cofilin in excitatory neurons |
| topic | neuropathic pain spinal cord excitatory neuron neuroligin1 cofilin GluR1 |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.640533/full |
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