scholarly journals Mechanisms Underlying Gastrodin Alleviating Vincristine-Induced Peripheral Neuropathic Pain

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Wang ◽  
Boxuan Zhang ◽  
Xuedong Li ◽  
Xingang Liu ◽  
Songsong Wang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sodium Channels ◽  
Thermal Hyperalgesia ◽  
Free Energies ◽  
Drg Neurons ◽  
Complex Action ◽  
Peripheral Neuropathic Pain ◽  
Over Expression ◽  
Chinese Herbal ◽  
Binding Free Energies

Gastrodin (GAS) is the main bioactive ingredient of Gastrodia, a famous Chinese herbal medicine widely used as an analgesic, but the underlying analgesic mechanism is still unclear. In this study, we first observed the effects of GAS on the vincristine-induced peripheral neuropathic pain by alleviating the mechanical and thermal hyperalgesia. Further studies showed that GAS could inhibit the current density of NaV1.7 and NaV1.8 channels and accelerate the inactivation process of NaV1.7 and NaV1.8 channel, thereby inhibiting the hyperexcitability of neurons. Additionally, GAS could significantly reduce the over-expression of NaV1.7 and NaV1.8 on DRG neurons from vincristine-treated rats according to the analysis of Western blot and immunofluorescence results. Moreover, based on the molecular docking and molecular dynamic simulation, the binding free energies of the constructed systems were calculated, and the binding sites of GAS on the sodium channels (NaV1.7 and NaV1.8) were preliminarily determined. This study has shown that modulation of NaV1.7 and NaV1.8 sodium channels by GAS contributing to the alleviation of vincristine-induced peripheral neuropathic pain, thus expanding the understanding of complex action of GAS as a neuromodulator.

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 A Case of Wasp-induced Pain Treated with Topical Phenytoin Cream

2018 ◽  
Vol 1 (3) ◽  
pp. 106-108
Author(s):  
M keppel Hesselink Jan ◽  
Keyword(s):  
Neuropathic Pain ◽  
Sodium Channels ◽  
Mechanism Of Action ◽  
Successful Treatment ◽  
Onset Of Action ◽  
Peripheral Neuropathic Pain ◽  
Wasp Sting ◽  
Competent Cells ◽  
First Time

Phenytoin cream has been evaluated in many patients suffering from peripheral neuropathic pain. Its onset of action has been documented to be within 30 minutes. Its mechanism of action is via the inhibition of sodium channels of the nociceptors in the skin, as well as the inhibition of a number of secondary targets in the skin, such as the keratinocytes and possibly immune-competent cells. Here we describe for the first time the successful treatment of lingering neuralgiformic pains after a wasp sting. Within 20 minutes after application of 10% phenytoin cream, the pain vanished completely. Phenytoin cream might therefore also be of use in the treatment of pain induced by stinging insects.

scholarly journals Effects of alkaloids on peripheral neuropathic pain: a review

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Chunhao Zhu ◽  
Ning Liu ◽  
Miaomiao Tian ◽  
Lin Ma ◽  
Jiamei Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Molecular Mechanisms ◽  
Herbal Medicines ◽  
New Drugs ◽  
Intractable Pain ◽  
Chinese Herbal Medicines ◽  
Peripheral Neuropathic Pain ◽  
Chinese Herbal ◽  
Toxicological Studies ◽  
Novel Drugs

Abstract Neuropathic pain is a debilitating pathological pain condition with a great therapeutic challenge in clinical practice. Currently used analgesics produce deleterious side effects. Therefore, it is necessary to investigate alternative medicines for neuropathic pain. Chinese herbal medicines have been widely used in treating intractable pain. Compelling evidence revealed that the bioactive alkaloids of Chinese herbal medicines stand out in developing novel drugs for neuropathic pain due to multiple targets and satisfactory efficacy. In this review, we summarize the recent progress in the research of analgesic effects of 20 alkaloids components for peripheral neuropathic pain and highlight the potential underlying molecular mechanisms. We also point out the opportunities and challenges of the current studies and shed light on further in-depth pharmacological and toxicological studies of these bioactive alkaloids. In conclusion, the alkaloids hold broad prospects and have the potentials to be novel drugs for treating neuropathic pain. This review provides a theoretical basis for further applying some alkaloids in clinical trials and developing new drugs of neuropathic pain.

scholarly journals Electroacupuncture Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Rats via Suppressing TLR4 Signaling and TRPV1 Upregulation in Sensory Neurons

2019 ◽  
Vol 20 (23) ◽  
pp. 5917 ◽  
Author(s):  
Yuanyuan Li ◽  
Chengyu Yin ◽  
Xiaojie Li ◽  
Boyu Liu ◽  
Jie Wang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Common Adverse Effect ◽  
Receptor Potential ◽  
Primary Response ◽  
Channel Activity ◽  
Trpv1 Channel ◽  
Drg Neurons ◽  
Tlr4 Signaling ◽  
Peripheral Neuropathic Pain

Paclitaxel-induced peripheral neuropathy is a common adverse effect during paclitaxel treatment resulting in sensory abnormalities and neuropathic pain during chemotherapy and in cancer survivors. Conventional therapies are usually ineffective and possess adverse effects. Here, we examined the effects of electroacupuncture (EA) on a rat model of paclitaxel-induced neuropathic pain and related mechanisms. EA robustly and persistently alleviated paclitaxel-induced pain hypersensitivities. Mechanistically, TLR4 (Toll-Like Receptor 4) and downstream signaling MyD88 (Myeloid Differentiation Primary Response 88) and TRPV1 (Transient Receptor Potential Vallinoid 1) were upregulated in dorsal root ganglion (DRGs) of paclitaxel-treated rats, whereas EA reduced their overexpression. Ca2+ imaging further indicated that TRPV1 channel activity was enhanced in DRG neurons of paclitaxel-treated rats whereas EA suppressed the enhanced TRPV1 channel activity. Pharmacological blocking of TRPV1 mimics the analgesic effects of EA on the pain hypersensitivities, whereas capsaicin reversed EA’s effect. Spinal astrocytes and microglia were activated in paclitaxel-treated rats, whereas EA reduced the activation. These results demonstrated that EA alleviates paclitaxel-induced peripheral neuropathic pain via mechanisms possibly involving suppressing TLR4 signaling and TRPV1 upregulation in DRG neurons, which further result in reduced spinal glia activation. Our work supports EA as a potential alternative therapy for paclitaxel-induced neuropathic pain.

scholarly journals Retrograde Labeling of Different Distribution Features of DRG P2X2 and P2X3 Receptors in a Neuropathic Pain Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Lin Chen ◽  
Changlong Leng ◽  
Qin Ru ◽  
Qi Xiong ◽  
Mei Zhou ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Rat Model ◽  
Dorsal Root ◽  
Chronic Constriction Injury ◽  
P2x Receptors ◽  
Drg Neurons ◽  
P2x3 Receptors ◽  
Peripheral Neuropathic Pain ◽  
Distribution Features

The distributions of P2X subtypes during peripheral neuropathic pain conditions and their differential roles are not fully understood. To explore these characteristics, the lumbosacral dorsal root ganglion (DRG) in the chronic constriction injury (CCI) sciatic nerve rat model was studied. Retrograde trace labeling combined with immunofluorescence technology was applied to analyze the distribution of neuropathic nociceptive P2X1-6 receptors. Our results suggest that Fluoro-Gold (FG) retrograde trace labeling is an efficient method for studying lumbosacral DRG neurons in the CCI rat model, especially when the DRG neurons are divided into small, medium, and large subgroups. We found that neuropathic nociceptive lumbosacral DRG neurons (i.e., FG-positive cells) were significantly increased in medium DRG neurons, while they declined in the large DRG neurons in the CCI group. P2X3 receptors were markedly upregulated in medium while P2X2 receptors were significantly decreased in small FG-positive DRG neurons. There were no significant changes in other P2X receptors (including P2X1, P2X4, P2X5, and P2X6). We anticipate that P2X receptors modulate nociceptive sensitivity primarily through P2X3 subtypes that are upregulated in medium neuropathic nociceptive DRG neurons and/or via the downregulation of P2X2 cells in neuropathic nociceptive small DRG neurons.

scholarly journals Neuroprotective and Anti-Inflammatory Activities of Atorvastatin in a Rat Chronic Constriction Injury Model

2012 ◽  
Vol 25 (1) ◽  
pp. 219-230 ◽  
Author(s):  
L.W. Chu ◽  
J.Y. Chen ◽  
K.L. Yu ◽  
K.I. Cheng ◽  
I.J. Chen ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Chronic Constriction Injury ◽  
Thermal Hyperalgesia ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Peripheral Neuropathic Pain ◽  
Anti Inflammatory ◽  
Coa Reductase

Atorvastatin is an HMG-CoA reductase inhibitor used to treat hypercholesterolemic conditions associated with hypertension. This study aims to investigate the anti-inflammatory and neuroprotective effects of atorvastatin on peripheral neuropathic pain. Peripheral neuropathic pain was induced by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats were divided into 3 groups including sham-operated, CCI, and atorvastatin-treated. Atorvastatin (10 mg/kg) or phosphate-buffered saline was orally administered for 2 weeks. All animals were assessed by neurobehavioral tests before surgery and at days 3, 7, 14 after surgery. Inflammatory and neuroprotective factors were evaluated by Western blot analysis. eNOS, COX2 and iNOS in the sciatic nerve were also studied using immunohistochemistry. Atorvastatin attenuated CCI-induced nociceptive sensitization and thermal hyperalgesia in a time-dependent manner. Atorvastatin improved CCI-induced neurobehavioral/inflammatory activity by inhibition of TGF-β, PIκB/IκB, NFκB, COX2, iNOS, EP1 and EP4 in the sciatic nerve. Atorvastatin was also found to increase neuroprotection factors pAkt/Akt, eNOS and VEGF. Taken together, these data indicate that atorvastatin could protect the sciatic nerve against CCI-induced neuroinflammation and nociception.

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.

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