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Papers of the Week


Papers: 12 Jan 2019 - 18 Jan 2019


Animal Studies


2019 05


Pain


160


5

SIRT1 alleviates diabetic neuropathic pain by regulating synaptic plasticity of spinal dorsal horn neurons.

Authors

Zhang Z, Ding X, Zhou Z, Qiu Z, Shi N, Zhou S, Du L, Zhu X, Wu Y, Yin X, Zhou C
Pain. 2019 05; 160(5):1082-1092.
PMID: 30649099.

Abstract

Accumulating evidence has demonstrated that the enhanced synaptic plasticity of nociceptive interneurons in the spinal dorsal horn is the basis of central sensitization in neuropathic pain. Our previous results demonstrate that Sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase, alleviates neuropathic pain in type 2 diabetes mellitus (T2DM) rats. SIRT1 has also been reported to regulate synaptic plasticity in different brain neurons. However, the role of SIRT1 in synaptic plasticity of spinal dorsal horn neurons remains unknown. In this study, we found that in the spinal dorsal horn of diabetic neuropathic pain (DNP) rats and db/db mice, decreased SIRT1 expression was accompanied by enhanced structural synaptic plasticity. The levels of post-synaptic density protein 95 (PSD-95), growth associated protein 43 (GAP43) and synaptophysin (SYP) increased in the spinal dorsal horn of DNP rats and db/db mice and in high glucose (HG)-cultured primary spinal neurons. Upregulation of spinal SIRT1 by SIRT1 activator SRT1720 relieved pain behavior, inhibited the enhanced structural synaptic plasticity in DNP rats and db/db mice, and decreased the levels of synapse-associated proteins in DNP rats, db/db mice, and HG-cultured spinal neurons. SIRT1 shRNA induced pain behavior, enhanced structural synaptic plasticity in normal rats, and increased synapse-associated proteins levels in normal rats and spinal neurons. Intrathecal AAV-Cre-EGFP into SIRT1 mice also induced pain behavior and enhanced synaptic plasticity of the spinal dorsal horn neurons. These results suggest that SIRT1 plays an important role in the progression of DNP by regulating synaptic plasticity of spinal dorsal horn neurons.