Frontiers in Neuroscience
·
2025
·
IF 3.2
Daxian Li,Yan Wu,Lirong Chang,Yizhi Song,Xiaoqiang Du,Fenqin Xue,Yang Liu,Jie Wu,Tianlong Wang
Introduction: As a taxane-based cytostatic agent, paclitaxel holds a broad spectrum of life-saving properties. However, its use is frequently limited by painful neuropathy in the extremities, which severely hinders the ultimate prognosis of cancer survivors. While bee venom therapy has shown promise in alleviating chemotherapy-induced neuropathic pain, the analgesic potential of its primary bioactive components, such as melittin and phospholipase A2 (bvPLA2), remains uncharacterized. This study investigated the ameliorative effects of melittin against paclitaxel-induced peripheral neuropathy in rats through integrated behavioral, in vivo electrophysiological, and neuropharmacological approaches.Methods: Paclitaxel was administered intraperitoneally (i.p.) at a total dose of 8 mg/kg. Cold and mechanical allodynia and hyperalgesia were quantified using the acetone drop and von Frey filament tests. To compare the therapeutic properties of bee venom ingredients, either melittin (0.5 mg/kg) or bvPLA2 (0.12 mg/kg) was administered subcutaneously at ST36 (Zusanli acupoint). In vivo extracellular recordings of wide dynamic range (WDR) neurons were performed in the spinal dorsal horn. Noradrenaline depletion was induced by the i.p. treatment with N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg/kg), and serotonin depletion was conducted by the i.p. administration of para-chlorophenylalanine (PCPA, 450 mg/kg).Results: ST36 treatment with melittin, but not bvPLA2, markedly impeded mechanical and cold hypersensitivity. Electrophysiological analysis revealed that paclitaxel induced spontaneous and stimulus-evoked hyperexcitation of spinal WDR neurons. Melittin selectively suppressed evoked neuronal activities (i.e., acute responses and after-discharges) without modulating the spontaneous firing of WDR neurons. Neuropharmacological investigation demonstrated that the effects of melittin were fully reversed by noradrenaline depletion, whereas serotonin depletion had no effect.Discussion: Our findings establish that melittin treatment at ST36 could ease paclitaxel-induced neuropathic pain by partially attenuating the hyperexcitable state of spinal WDR neurons. Furthermore, these ameliorative actions were mediated by the specific recruitment of the endogenous noradrenergic system. This study provides novel evidence supporting melittin as a targeted symptomatic agent for paclitaxel-induced peripheral neuropathy, which would advance the development of promising analgesic strategies in oncological care.
研究领域:
药理学
·
神经科学
·
肿瘤学
·
生物医学
✓ 已验证
DOI
PubMed
高影响因子
Purinergic Signalling
·
2020
·Vol. 16
·期 4
·585-599
·
IF 3.065
Ge Huixiang,Sun Mengyun,Wei Xingyu,Zhang Mingming,Tu Hongcheng,Hao Yuanzhen,Chen Ruxin,Ye Miao,Gao Yun
Activated astrocytes play a key role in diabetic neuropathic pain and depression. We aimed to assess the protective effects of dihydromyricetin (DHM) on primary hippocampal astrocytes cultured with high glucose (HG), substance P (SP), and corticosterone (CORT). Culturing with HG + SP + CORT resulted in damage to primary hippocampal astrocytes, which simulates the clinical damage caused by comorbidity of diabetic neuropathic pain and depression. Western blot, qPCR, and immunofluorescence analyses revealed that HG + SP + CORT increased P2X 7 receptor expression in primary hippocampal astrocytes, which was reversed by DHM treatment. Further, HG + SP + CORT elevated TNF-α, IL-1β, free Ca 2+ , and ERK1/2 phosphorylation levels, which was inhibited by DHM or P2X 7 shRNA treatment. Moreover, DHM significantly reduced the P2X 7 agonist-activated currents in HEK293 cells transfected with the P2X 7 receptor. These findings suggest that DHM can protect primary hippocampal astrocytes cultured with HG + SP + CORT from P2X 7 receptor-mediated damage. Culturing cells with HG + SP + CORT might be a viable cell model for cellular injury exploration of diabetic comorbid pain and depression.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Di Zhang,Bei Jing,Zhenni Chen,Xin Li,Huimei Shi,Yachun Zheng,Shiquan Chang,Guoping Zhao
Background Nonsteroidal anti-inflammatory drugs are used to relieve sciatica, but their effects are not satisfactory. Purpose This study aimed to explore the therapeutic effects of ferulic acid on sciatica. Methods Thirty-two SD rats were randomly divided into 4 groups, i.e., sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and ferulic acid group. We conducted behavioural tests, ELISA, PCR, Western blots, and immunofluorescence analysis. Specific inhibitors were used in cell experiments to explore the related mechanisms. Results Thermal hyperalgesia was induced after CCI operation, and ferulic acid relieved thermal hyperalgesia. In addition, ferulic acid decreased the IL1β, IL6, TNF-α, and CRP mRNA levels; the IBA-1, iNOS, IL1β, RhoA, RhoA-GTP, COX2, Rock1, TRPV1, TRPA1, and p-p38MAPK levels in dorsal root ganglion (DRG) neurons; and the LPS, CRP, substance P (SP), and prostaglandin E2 (PGE2) levels in serum, and these levels were higher in the CCI group. In the cell experiments, LPS induced M1 polarization of GMI-R1 cells via the RhoA/Rock pathway. Ferulic acid attenuated LPS-induced M1 polarization by decreasing the levels of M1 polarization markers, including IL1β, IL6, TNF-α, iNOS, and CD32, and increased M2 polarization by increasing the levels of M2 polarization markers, including CD206 and Arg-1. LPS treatment clearly increased the iNOS, IL1β, RhoA, Rock1, Rock2 and p-p38 MAPK levels and reduced Arg-1 expression, and ferulic acid reversed these changes. Conclusion Ferulic acid can inhibit peripheral sensitization by reducing the levels of inflammatory factors, TRPA1 and TRPV1 through the RhoA/p38 MAPK pathway to alleviate sciatica.
研究领域:
药理学
·
神经科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Zhang Di,Chen Zhenni,Zhuang Zifeng,Jing Bei,Cao Yong,Li Yixuan,Pan Yuwei,Gao Li,Chen Jiaxu,Zhao Guoping
Ethnopharmacological relevance Danggui Sini Decoction (DGSD), which is commonly used to treat sciatica, has been shown to have an analgesic effect, but the underlying mechanisms are unclear. Here, Danggui Sini Decoction was shown to normalize the intestinal microbiota and serum metabolite levels to exert an analgesic effect. Aim of the study This study aimed to elucidate the therapeutic effects of DGSD on sciatica and the underlying mechanisms involved. Methods In this study, we conducted chronic constriction injury (CCI) model. Mecobalamin and DGSD were administered to CCI rats. Behavioural tests were used to examine the therapeutic effects of the drugs. UHPLC was used to identify DGSD components. 16S rRNA gene sequencing analysis of the intestinal flora was used to analyse the effect of DGSD on the intestinal microbiota. UHPLC‒MS/MS was used to identify blood metabolites. KEGG pathway analysis of differentially abundant metabolites was subsequently conducted. ELISA was used to measure the serum inflammatory factor levels, and correlation analysis between the serum inflammatory factor levels and intestinal microbe abundance was conducted. PCR, western blotting, and immunohistochemical staining were used to validate the results of the KEGG pathway analysis. Results After CCI, the rats exhibited obvious thermal hyperalgesia; disruption of sciatic nerve structure; increased IL1α, SP, CCL5, and PGE2 levels; decreased IL10 levels in the blood; increased IL1β, IL6, COX2, MMP9, nNOS, and p-NF-κB levels; and decreased IL4 levels in the sciatic nerve. In addition, CCI led to increased abundances of Peptostreptococcaceae, Leuconostocaceae, Christensenellaceae, Akkermansiaceae, Staphylococcaceae, Romboutsia, Marvinbryantia, Turicibacter, Weissella, UCG-005, Christensenellaceae_R-7_group, Akkermansia, Staphylococcus, Romboutsia_ilealis, Weissella_paramesenteroides, and Akkermansia_muciniphila and decreased abundances of Lactobacillaceae, Lactobacillus, Lactobacillus_murinus, and Lactobacillus_johnsonii. Correlation analysis indicated that Turicibacter abundance was most strongly related to IL1α, PGE2, IL10, and CCL5 levels, while norank_o_Coriobacteriales abundance had the weakest relationship with SP levels. KEGG pathway analysis of the differentially abundant metabolites revealed that the ‘NF-kappa B signalling pathway’ was involved in sciatica. DGSD reduced the levels of inflammatory factors, including IL1α, SP, CCL5, PGE2, IL6, COX2, and MMP9, in the blood and sciatic nerve and inhibited nNOS and NF-κB phosphorylation. DGSD improved the abundance of probiotics, including Lactobacillus and Blautia, and lowered the abundance of harmful bacteria, including Romboutsia, Turicibacter, and Weissella. DGSD promoted the repair of the injured sciatic nerve. Conclusions DGSD can treat sciatica by inhibiting intestinal microbiota disorders induced by CCI in rats, normalizing inflammatory factor levels, and promoting nerve repair.
研究领域:
药理学
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神经科学
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微生物学
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代谢组学
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民族药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Xu Xiong,Chang Shuai,Zhang Xiaoyi,Hou Taotao,Yao Hui,Zhang Shusheng,Zhu Yuqi,Cui Xu,Wang Xing
Lidocaine, a potent local anesthetic, is clinically used in nerve block and pain management. However, due to its short half-life, repeated administration is required. For this reason, here we designed and prepared a lidocaine-encapsulated polylactic acid-glycolic acid (Lidocaine@PLGA) microcapsule with ultrasound responsiveness to relieve the sciatica nerve pain. With a premixed membrane emulsification strategy, the fabricated lidocaine-embedded microcapsules possessed uniform particle size, good stability, injectability, and long-term sustained release both in vitro and in vivo. More importantly, Lidocaine@PLGA microcapsules had the function of ultrasonic responsive release, which made the drug release controllable with the effect of on-off administration. Our research showed that using ultrasound as a trigger switch could promote the rapid release of lidocaine from the microcapsules, achieving the dual effects of long-term sustained release and short-term ultrasound-triggered rapid release, which can enable the application of ultrasound-responsive Lidocaine@PLGA microcapsules to nerve root block and postoperative pain relief.
研究领域:
药学
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药物递送系统
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疼痛管理
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Oral & Facial Pain and Headache
·
2024
·Vol. 38
·期 1
·77
·
IF 1.9
Zhiheng Feng,Mingcai Chen,Jue Zhang,Xin Peng
Pain assessment in trigeminal neuralgia (TN) mouse models is essential for exploring its pathophysiology and developing effective analgesics. However, pain assessment methods for TN mouse models have not been widely studied, resulting in a critical gap in our understanding of TN. With the rapid advancement of deep learning, numerous pain assessment methods based on deep learning have emerged. Nonetheless, these methods have some limitations: (1) insufficiently objective supervision signals for training, (2) failure to account for the dynamic behavioral characteristics of mouse models in the constructed models and (3) inadequate generalization ability of the models. In this study, we initially constructed an objective pain grading dataset as the ground truth for model training, which remedy the limitations of prior studies that relied on subjective evaluation as supervisory signals. Then we proposed a novel deep neural network, named trigeminal neuralgia pain assessment network (TNPAN), which fuses the static texture characteristics and dynamic behavioral characteristics of mouse facial expressions. The promising experimental results demonstrate that TNPAN exhibits exceptional accuracy and generalization capability in pain assessment.
研究领域:
神经科学
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疼痛研究
·
深度学习
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医学影像
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行为分析
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
METABOLISM-CLINICAL AND EXPERIMENTAL
·
2015
·
IF 3.894
Qian Huang,Yuan Chen,Nian Gong,Yong-Xiang Wang
Objective Methylglyoxal is known to be associated with the development of nephropathy , retinopathy , and other complications in diabetes. The present study tested the hypothesis that endogenously increased levels of methylglyoxal in diabetes are causally associated with the induction of neuropathic pain . Materials and methods Streptozotocin- and methylglyoxal-induced pain models were established in rats, and the anti-nociceptive effects of the methylglyoxal scavenging agents, selective transient receptor potential channel ankyrin 1 (TRPA1) antagonist, and Nav1.8 antagonist were tested. Results Systemic injection of streptozotocin in rats induced a prolonged increase in plasma methylglyoxal by approximately 60%, which was correlated with the progressive development of mechanical allodynia and thermal hyperalgesia . Local subcutaneous injection of methylglyoxal into the hindpaw produced dose-dependent and biphasic flinching nociceptive responses, which resembled formaldehyde (formalin)-induced nociception . The local methylglyoxal nociception was significantly blocked by co-injection into the hindpaw of the selective transient receptor potential channel ankyrin 1 (TRPA1) antagonist, A967079, and the Nav1.8 antagonist, A803467. Co-incubation with the methylglyoxal scavengers, aminoguanidine , d -arginine, and metformin , reduced the level of free methylglyoxal by more than 90%, and injection of their incubation solutions into the hindpaw produced negligible (3–17%) nociception. Like the clinically effective anti-diabetic neuropathic pain drug gabapentin , systemic injection of aminoguanidine, d -arginine, and metformin at doses that effectively inhibit paw-injected methylglyoxal-induced nociception significantly blocked streptozotocin-induced mechanical allodynia. Conclusion Endogenously increased methylglyoxal may mediate diabetic neuropathic pain via activation of both TRPA1 and Nav1.8 expressed on primary afferent sensory neurons , and injection of methylglyoxal into the hindpaw may serve as a simple and robust model for testing the anti-diabetic pain drugs.
研究领域:
药理学
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神经科学
·
糖尿病研究
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疼痛管理
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL TRANSPLANTATION
·
2022
·
IF 4.139
Wan Wei,Qiuhong Yang,Jing Hu,Yong Yao,Huayuan Yang
The physicochemical stimulation of acupoints is a widespread treatment strategy for different diseases, such as sciatica. Its efficacy is mainly based on the temporal and spatial modulation of the physicochemical properties of the acupoints. The existing therapies based on the stimulation of acupoints have certain disadvantages. Therefore, in this study, injectable dexamethasone (DXM)- and magnetic Fe3O4 nanoparticles-loaded chitosan/β-glycerophosphate (CS/GP) thermal crosslinking hydrogels were prepared, thereby improving the performance of embedding materials. The sciatica rat models were established to compare the therapeutic effects of hydrogels and catgut. The DXM or Fe3O4-loaded CS/GP hydrogels were compared in terms of their gelation kinetics, release kinetics, magnetic responsiveness in-vitro, and biocompatibility as well as their analgesic effects on the chronic constriction injury of the sciatic nerve (CCI) rats in-vivo. The CS/GP/Fe3O4/DXM hydrogel showed comparable gelation kinetics and good magnetic responsiveness in-vitro. This hydrogel could relieve sciatica by reducing the expression levels of inflammatory factors in serum, inhibiting the p38MAPK (p38, mitogen-activated protein kinase) phosphorylation, and decreasing the expression level of the P2X4 receptor (P2X4R) in the spinal dorsal horn. In conclusion, the DXM or Fe3O4-loaded CS/GP hydrogels can be considered as a treatment option for the physiochemical stimulation therapy of acupoints to improve sciatica.
研究领域:
药理学
·
材料科学
·
神经科学
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生物医学工程
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Kaichao Song,Yumei Hao,Xiaochuan Tan,Hongdong Huang,Lulu Wang,Wensheng Zheng
Ziconotide (ZIC) is an N-type calcium channel antagonist for treating severe chronic pain that is intolerable, or responds poorly to the administration of other drugs, such as intrathecal morphine and systemic analgesics. As it can only work in the brain and cerebrospinal fluid , intrathecal injection is the only administration route for ZIC. In this study, borneol (BOR)-modified liposomes (LIPs) were fused with exosomes from mesenchymal stem cells (MSCs) and loaded with ZIC to prepare microneedles (MNs) to improve the efficiency of ZIC across the blood-brain barrier. To evaluate local analgesic effects of MNs, the sensitivity of behavioral pain to thermal and mechanical stimuli was tested in animal models of peripheral nerve injury , diabetes-induced neuropathy pain, chemotherapy-induced pain, and ultraviolet-B (UV-B) radiation-induced neurogenic inflammatory pain . BOR-modified LIPs loaded with ZIC were spherical or nearly spherical, with a particle size of about 95 nm and a Zeta potential of −7.8 mV. After fusion with MSC exosomes, the particle sizes of LIPs increased to 175 nm, and their Zeta potential increased to −3.8 mV. The nano-MNs constructed based on BOR-modified LIPs had good mechanical properties and could effectively penetrate the skin to release drugs. The results of analgesic experiments showed that ZIC had a significant analgesic effect in different pain models. In conclusion, the BOR-modified LIP membrane-fused exosome MNs constructed in this study for delivering ZIC provide a safe and effective administration for chronic pain treatment, as well as great potential for clinical application of ZIC.
研究领域:
药学
·
纳米技术
·
神经科学
·
疼痛管理
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·Vol. 29
·期 4
·1000-1011
·
IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
·
细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）