Shank3 contributes to neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95.

Abstract:

:Neuropathic pain is a very complex chronic pain state, the detailed molecular mechanisms of which remain unclear. In the present study, Shank3 was found to play an important role in neuropathic pain in rats following spared nerve injury (SNI). Shank3 was upregulated in the spinal dorsal horn of rats subjected to SNI, and mechanical hypersensitivity to noxious stimuli in these rats could be alleviated by knock down of Shank3. Shank3 also interacted with hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and promoted the expression of HCN2 in central neurons of the spinal dorsal. Together with the SNI-dependent increase of HCN2, we also found that the postsynaptic protein of excitatory synapse (PSD95) was increased in rats following SNI. Taken together, our results showed that Shank3 modulated neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95 in spinal dorsal horn neurons. Our findings revealed new synaptic remodeling mechanisms linking Shank3 with neuropathic pain.

journal_name

Neurosci Res

journal_title

Neuroscience research

authors

Zhang X,Li X,Wang H,Xie X,Li Y,Xu X,Su S,Zhao H,Li J,Ke C,Liu J

doi

10.1016/j.neures.2020.05.010

subject

Has Abstract

pub_date

2020-05-23 00:00:00

eissn

0168-0102

issn

1872-8111

pii

S0168-0102(20)30165-6

pub_type

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