The spinal notch signaling pathway plays a pivotal role in the development of neuropathic pain

Yan-Yan Sun,Nan Gu,Hai-Long Dong,Lize Xiong,Li Li,Xiao-Hua Liu

doi:10.1186/1756-6606-5-23

Yan-Yan Sun, Nan Gu + Show 4 more

Open Access

https://doi.org/10.1186/1756-6606-5-23

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Journal: Molecular brain	Publication Date: Jun 19, 2012
Citations: 51	License type: cc-by

Affiliation: Air Force Medical University, Xijing Hospital

Abstract

BackgroundThe Notch signaling pathway has been shown to be involved in the development of the nervous system. Recent studies showed that Notch receptors and ligands are also expressed in the nervous system of adult animals. However, whether the Notch signaling pathway has a function in adults is not fully understood. The present study is designed to investigate the function of the Notch signaling pathway in nociceptive transmission, especially during neuropathic pain in adult rats.ResultsWe found that the Notch intracellular domain (NICD) is expressed in the DRG (Dorsal Root Ganglia), sciatic nerve and spinal cord in normal rats, and is upregulated in the sciatic nerve and spinal cord after spared nerve injury (SNI). Moreover, we used the γ-secretase (a key enzyme of the Notch signaling pathway) inhibitor DAPT to observe the effect of the Notch signaling pathway after SNI. We found that intrathecal DAPT significantly increased paw withdrawal thermal latency and mechanical threshold. Mechanical hyperalgesia occurring after SNI could be significantly reversed by DAPT in a dose-dependent manner.ConclusionsThese results suggest that the Notch signaling pathway participates in the induction and maintenance of neuropathic pain, which indicates that the Notch pathway maybe a potential drug target for neuropathic pain treatment.

Highlights

The Notch signaling pathway has been shown to be involved in the development of the nervous system
Our present study shows that Notch intracellular domain (NICD) expression in the rat sciatic nerve and dorsal horn of the spinal cord is markedly increased following peripheral nerve injury
Seven days after induction of the unilateral CCI (Sciatic Nerve Chronic Constriction Injury Model) model, immunoblot analyses showed that NICD protein levels in the dorsal horn of the spinal cord increased to ~168.3% of the control (Figure 1A)

Summary

Results

We found that the Notch intracellular domain (NICD) is expressed in the DRG (Dorsal Root Ganglia), sciatic nerve and spinal cord in normal rats, and is upregulated in the sciatic nerve and spinal cord after spared nerve injury (SNI). We used the γ-secretase (a key enzyme of the Notch signaling pathway) inhibitor DAPT to observe the effect of the Notch signaling pathway after SNI. We found that intrathecal DAPT significantly increased paw withdrawal thermal latency and mechanical threshold. Mechanical hyperalgesia occurring after SNI could be significantly reversed by DAPT in a dose-dependent manner

Background

Results and discussion

Conclusion

Materials and methods

Woolf CJ