Tanshinone IIA Improves Painful Diabetic Neuropathy by Suppressing the Expression and Activity of Voltage-Gated Sodium Channel in Rat Dorsal Root Ganglia

Ao Ri-Ge-le; Zhuang-Li Guo; Qi Wang; Bao-Jian Zhang; Da-Wei Kong; Wen-Qiang Yang; Yan-Bing Yu; Li Zhang

doi:10.1055/s-0044-100722

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2018; 126(10): 632-639
DOI: 10.1055/s-0044-100722

Article

Tanshinone IIA Improves Painful Diabetic Neuropathy by Suppressing the Expression and Activity of Voltage-Gated Sodium Channel in Rat Dorsal Root Ganglia

Ao Ri-Ge-le

¹Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China

²Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China

,

Zhuang-Li Guo

³Department of Rehabilitation, The Affiliated Hospital of Qingdao University, Qingdao, China

,

Qi Wang

¹Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China

,

Bao-Jian Zhang

¹Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China

,

Da-Wei Kong

¹Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China

,

Wen-Qiang Yang

²Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China

,

Yan-Bing Yu

¹Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China

²Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China

,

Li Zhang

¹Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China

²Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China

› Author Affiliations

Abstract

Painful diabetic neuropathy (PDN) is one of the intractable complications of diabetes mellitus, which manifest as exaggerated pain perception. Previous studies showed that Tanshinone IIA (TIIA), one of the major bioactive extracts of Salvia miltiorrhiza Bunge, have obvious analgesic effect on different types of pain process, and the underlying analgesic mechanisms are not fully understood. The present study combined the behavioral, electrophysiological and biochemical methods to elucidate the analgesic mechanism of TIIA, using streptozotocin (STZ)-induced PDN rat models. Intraperitoneal injection (i.p.) of TIIA for 3 weeks in PDN rats significantly improved mechanical allodynia and thermal hyperalgesia. Patch clamp recordings showed that the excitability of dorsal root ganglion (DRG) nociceptive neuron was increased in diabetic state, and TIIA treatment effectively recovered the subnormality, which was achieved by preventing augments of both Tetrodotoxin-sensitive (TTX-resistant) and Tetrodotoxin-sensitive (TTX-S) sodium currents. Further, the protein expressions of voltage-gated sodium channels (VGSCs) α-subunits Nav1.3, Nav1.7 and Nav1.9 increased in DRG of diabetic rats and were normalized by TIIA application. In conclusion, this study provides evidence that the TIIA attenuated PDN by effecting VGSCs activities and expressions, indicating that the TIIA could be a promising agent for PDN treatment.

Key words

Tanshinone IIA - Painful diabetic neuropathy - Pain perception - voltage-gated sodium channels - neuronal excitability

Full Text

References

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