Background & Aims

Neuropathic pain is a clinically common disease that is difficult to treat. Because of severe pain and recurrent symptoms of neuropathic pain which can cause lead to depression in some patients. Although NP-depression comorbidity has attracted widespread attention, the neural mechanism of NP-depression comorbidity is still unclear. The excitability of lateral habenula (LHb) neurons is closely related to pain and negative emotions. T-type calcium channel, as a member of the calcium ion channel family, can participate in the regulation of neuronal excitability, abnormal expression and functional changes of T-type calcium channels will lead to pain and negative emotions. Whether T-type calcium channels in LHb involved in the regulation of NP-depression comorbidity?

Methods

C57BL/6J wild-type mice were selected to establish SNC and Sham model mice, and the mechanical pain threshold was tested before and after operation. Depression and exercise-related behaviors were measured after operation to clarify the occurrence time of NP-depression comorbidity in the SNC model. In vitro electrophysiological experiments were performed on the two groups of mice at 8 w postoperatively to observe the excitability of LHb neurons and the functional changes of T-type calcium channels. Mibefradil was used to observe the changes of LHb neurons excitability and the functional of T-type calcium channels in electrophysiological experiments. At the same time, the changes of pain, depression and motor behavior of mice in the two groups were observed after local administration of mibefradil to LHb neurons after intracranial cannulation.

Results

(1) The SNC model developed hyperalgesia on the third day and maintained it until 10 w postoperatively. Depressive-like behavior appeared at 8 w and it still existed after 10 w postoperatively. The SNC model did not affect its motor function.
(2) Compared with mice in Sham group, the excitability of neurons increased in the NP-depression comorbidity state in vitro electrophysiological experiments.
(3) The IT amplitude and current density of T-type calcium current in SNC mice were significantly increased in the NP-depression comorbidity compared with Sham group mice.
(4) Mibefradil can significantly reduce the excitability of LHb neurons and the amplitude and current density of IT.
(5) After local administration of Mibefradil, the mechanical hyperalgesia and depression-like behaviors of the mice in the SNC group could be significantly relieved and had no effect on the motor function of the mice in the two groups.

Conclusions

The SNC model can cause the occurrence of NP-depression comorbidity and the T-type calcium channel of LHb neurons is an ion channel which involved in the formation of NP-depression comorbidity and the regulation of pain and depression. T-type calcium channel is an important target for the treatment of NP-depression comorbidity.

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Presenting Author

Gang Xu

Poster Authors

Gang Xu

Ph.D

The First Affiliated Hospital of Nanchang University

Lead Author

E-mail

Daying Zhang

The First Affiliated Hospital of Nanchang University

Lead Author

E-mail

Tao Liu PhD

The First Affiliated Hospital of Nanchang University

Lead Author

E-mail

Mengye Zhu

The First Affiliated Hospital of Nanchang University

Lead Author

E-mail

Topics

  • Mechanisms: Biological-Molecular and Cell Biology