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

2018 ◽  
Vol 126 (10) ◽  
pp. 632-639
Author(s):  
Ao Ri-Ge-le ◽  
Zhuang-Li Guo ◽  
Qi Wang ◽  
Bao-Jian Zhang ◽  
Da-Wei Kong ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Dorsal Root ◽  
Pain Perception ◽  
Salvia Miltiorrhiza ◽  
Thermal Hyperalgesia ◽  
Diabetic Rats ◽  
Tanshinone Iia ◽  
Painful Diabetic Neuropathy ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels

AbstractPainful 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.

scholarly journals Tanshinone IIA Attenuates Diabetic Peripheral Neuropathic Pain in Experimental Rats via Inhibiting Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Baojian Zhang ◽  
Yanbing Yu ◽  
Gele Aori ◽  
Qi Wang ◽  
Dawei Kong ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Pain Perception ◽  
Mrna Level ◽  
Thermal Hyperalgesia ◽  
Diabetic Rats ◽  
Tanshinone Iia ◽  
Peripheral Neuropathic Pain ◽  
Novel Drugs ◽  
Anti Inflammatory

Diabetic peripheral neuropathic pain (DPNP) is a common and intractable complication of diabetes. Conventional therapies are always not ideal; development of novel drugs is still needed to achieve better pain relief. Recent evidences have demonstrated that inflammation is involved in the onset and maintenance of DPNP. The anti-inflammatory property of Tanshinone IIA (TIIA) makes it a promising candidate to block or alter the pain perception. This study was conducted to investigate whether TIIA could attenuate DPNP in streptozotocin- (STZ-) induced rats model and its potential mechanisms. TIIA was administered to STZ-induced diabetic rats at the dose of 40 mg/kg once a day for 3 weeks. The effects of TIIA on thermal hyperalgesia and mechanical allodynia were investigated using behavioral tests. The mRNA level and expression of interleukin- (IL-) 1β, interleukin- (IL-) 6, tumor necrosis factor- (TNF-)α, and interleukin- (IL-) 10 in the fourth to sixth segments of the dorsal root ganglion (L4–6 DRG) were detected by quantitative real-time PCR (qPCR) and Western blot. TIIA treatment significantly attenuated mechanical allodynia and thermal hyperalgesia in diabetic rats. In addition, the expression of the proinflammatory cytokines IL-1β, IL-6, and TNF-αwas inhibited, and the level of the anti-inflammatory cytokine IL-10 was increased by TIIA. This study demonstrated that TIIA has significant antiallodynic and antihyperalgesic effects in a rat model of STZ-induced DPNP, and the effect may be associated with its anti-inflammation property.

scholarly journals NEUROPROTECTION OF ABELMOSCHUS ESCULENTUS L. AGAINST DIABETIC NEUROPATHY

2018 ◽  
Vol 11 (15) ◽  
pp. 28
Author(s):  
Lee Wei Yang ◽  
Santosh Fattepur ◽  
Kiran Chanabasappa Nilugal ◽  
Fadli Asmani ◽  
Eddy Yusuf ◽  
...  
Keyword(s):  
Body Weight ◽  
Sciatic Nerve ◽  
Diabetic Neuropathy ◽  
Performance Test ◽  
Neuroprotective Effect ◽  
Thermal Hyperalgesia ◽  
Diabetic Rats ◽  
Nerve Fibers ◽  
Abelmoschus Esculentus ◽  
Rotarod Performance

Objective: The present study was designed to determine the neuroprotective effect of Abelmoschus esculentus L. on alloxan-induced diabetic neuropathy in rats.Methods: Diabetes was induced in rats with a single intraperitoneal injection of alloxan monohydrate (130 mg/kg b.w). The ethanol extract of A. esculentus L. at a dose of 100 and 200 mg/kg of body weight was administered at single dose per day to alloxan-induced diabetic rats for 21 days. The fasting blood glucose was screened in the intermittent on day 0, day 14, and day 21. Behavioral tests such as thermal hyperalgesia test and rotarod performance test were performed to assess the thermal sensitivity and muscle grip strength. At the end of the study period, experimental animals were sacrificed and sciatic nerve tissues were obtained for histopathological investigation.Results: Animals treated with A. esculentus L. extarct at a dose of 200 mg/kg of body weight significantly reduced (p<0.05) in hyperglycemia and thermal hyperalgesia and significantly increased (p<0.05) in rotarod performance. The sciatic nerve fiber of diabetic rats receiving 200 mg/kg of body weight of A. esculentus L. extract also shows no swelling of nerve fibers, and lesser demyelination was observed.Conclusion: These findings demonstrate that A. esculentus L. exhibits significant antidiabetic and neuroprotective effect against alloxan-induced diabetic neuropathy in rats.

scholarly journals Electroacupuncture Reduces Carrageenan- and CFA-Induced Inflammatory Pain Accompanied by Changing the Expression of Nav1.7 and Nav1.8, rather than Nav1.9, in Mice Dorsal Root Ganglia

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chun-Ping Huang ◽  
Hsiang-Ni Chen ◽  
Hong-Lin Su ◽  
Ching-Liang Hsieh ◽  
Wei-Hsin Chen ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Dorsal Root Ganglia ◽  
Inflammatory Pain ◽  
Dorsal Root ◽  
Low Frequency ◽  
Thermal Hyperalgesia ◽  
Nerve Fibers ◽  
Drg Neurons ◽  
Plantar Surface ◽  
Voltage Gated Sodium Channels

Several voltage-gated sodium channels (Navs) from nociceptive nerve fibers have been identified as important effectors in pain signaling. The objective of this study is to investigate the electroacupuncture (EA) analgesia mechanism by changing the expression of Navs in mice dorsal root ganglia (DRG). We injected carrageenan and complete Freund's adjuvant (CFA) into the mice plantar surface of the hind paw to induce inflammation and examined the antinociception effect of EA at the Zusanli (ST36) acupoint at 2 Hz low frequency. Mechanical hyperalgesia was evaluated by using electronic von Frey filaments, and thermal hyperalgesia was assessed using Hargreaves' test. Furthermore, we observed the expression and quality of Navs in DRG neurons. Our results showed that EA reduced mechanical and thermal pain in inflammatory animal model. The expression of Nav1.7 and Nav1.8 was increased after 4 days of carrageenan- and CFA-elicited inflammatory pain and further attenuated by 2 Hz EA stimulation. The attenuation cannot be observed in Nav1.9 sodium channels. We demonstrated that EA at Zusanli (ST36) acupoint at 2 Hz low-frequency stimulation attenuated inflammatory pain accompanied by decreasing the expression of Nav1.7 and 1.8, rather than Nav1.9, sodium channels in peripheral DRG neurons.

scholarly journals Inhibition of phosphorylated calcium/calmodulin-dependent protein kinase IIα relieves streptozotocin-induced diabetic neuropathic pain through regulation of P2X3 receptor in dorsal root ganglia

2022 ◽  
Author(s):  
Xiao-fen He ◽  
Yu-rong Kang ◽  
Xue-yu Fei ◽  
Lu-hang Chen ◽  
Xiang Li ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Fasting Blood Glucose ◽  
Thermal Hyperalgesia ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Diabetic Neuropathic Pain ◽  
Calcium Calmodulin Dependent ◽  
Patients With Diabetes

Abstract  Diabetic neuropathic pain (DNP) is frequent among patients with diabetes. We previously showed that P2X3 upregulation in dorsal root ganglia (DRG) plays a role in streptozotocin (STZ)-induced DNP but the underlying mechanism is unclear. Here, a rat model of DNP was established by a single injection of STZ (65 mg/kg). Fasting blood glucose was significantly elevated from the 1st to 3rd week. Paw withdrawal thresholds (PWTs) and paw withdrawal latencies (PWLs) in diabetic rats significantly reduced from the 2nd to 3rd week. Western blot analysis revealed that elevated p-CaMKIIα levels in the DRG of DNP rats were accompanied by pain-associated behaviors while CaMKIIα levels were unchanged. Immunofluorescence revealed significant increase in the proportion of p-CaMKIIα immune positive DRG neurons (stained with NeuN) in the 2nd and 3rd week and p-CaMKIIα was co-expressed with P2X3 in DNP rats. KN93, a CaMKII antagonist, significantly reduce mechanical hyperalgesia and thermal hyperalgesia and these effects varied dose-dependently, and suppressed p-CaMKIIα and P2X3 upregulation in the DRGs of DNP rats. These results revealed that the p-CaMKIIα upregulation in DRG is involved in DNP, which possibly mediated P2X3 upregulation, indicating CaMKIIα may be an effective pharmacological target for DNP management.

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