scholarly journals Dexmedetomidine Alleviates Hyperalgesia in Arthritis Rats Through Inhibition of the p38MAPK Signaling Pathway

2021 ◽  
Author(s):  
Bin Nie ◽  
Hui Jiang ◽  
Hong Chen ◽  
Qiong Liu
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Underlying Mechanism ◽  
Inflammatory Factors ◽  
Pathological Changes ◽  
Related Factors ◽  
Withdrawal Threshold ◽  
Analgesic Effects ◽  
Joint Cavity ◽  
P38mapk Signaling

Abstract Background: Dexmedetomidine (DEX) has showed significant analgesic effects in neuropathic pain, but the underlying mechanism has remained elusive. Our present study aimed to explore the effect of DEX on hyperalgesia with the involvement of p38MAPK signaling pathway a rat model of monoarthritis (MA).Methods: MA rat model was induced by injection of Complete Freund's Adjuvant (CFA). Pathological changes of ma rats were observed by HE staining and Safranin-O/Fast Green staining. Ankle circumference, paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) was measured to judge the degree of hyperalgesia in MA rats. Immunohistochemistry and ELISA were applied to observe the degree of inflammation in rats. Western blot analysis was conducted to detect expression of p38MAPK signaling pathway-related factors. The mechanism of p38MAPK signaling pathway in MA rats was observed via treatment of Anisomycin or SB203580 combined with DEX.Results: After 8 h of CFA induction, joint swelling and hyperalgesia occurred in rats. There were obvious pathological changes in the joint cavity, the joint cavity space became narrow and synovial bursa became rough. A large number of inflammatory cell infiltration was observed under microscope. After injection of DEX and SB203580, PWT and PWL was prolonged, the expression of serum inflammatory factors was decreased, and the expression of p38MAPK signaling pathway-related factors was decreased; while all the detected indexes were recovered in MA rats after treated with DEX and Anisomycin.Conclusions: Our study provided evidence that DEX could alleviate hyperalgesia in arthritis rats through inhibition of the p38MAPK signaling pathway.

scholarly journals Propofol Alleviates Neuropathic Pain Induced by Chronic Contractile Injury by Regulating the Spinal glun2b-p38mapkepac1 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Wen Li ◽  
Chenguang Qin ◽  
JianYong Yan ◽  
Qian Zhao ◽  
Lu You ◽  
...  
Keyword(s):  
Mechanical Allodynia ◽  
Underlying Mechanism ◽  
Histopathological Analysis ◽  
Immunofluorescence Analysis ◽  
Withdrawal Threshold ◽  
Analgesic Effects ◽  
Isoflurane Group ◽  
Dorsal Horns ◽  
Patients Experience ◽  
Thigh Region

Background. Propofol acts as an intravenous anesthetic cure which is widely used as a therapy for the craniocerebral injury that comprised surgical anesthesia as well as the sedation done in the intensive care units. Propofol is one of the most commonly used and efficient anesthetics where the painful effects are followed by an injection of propofol. In many cases, patients experience pain followed by anxiety, boredom, fear, and even myocardial ischemia. Objective. This study was performed to investigate the underlying mechanism of propofol and its effect on regulating spinal glun2b-p38mapkepac1 pathways in chronic contractile injury. Material and Methods. Contractile injury was performed by ligation around the nerve of the thigh region postanesthesia. Rats were divided into three groups to analyze the changes like mechanical allodynia by the paw withdrawal threshold and histopathological analysis for assessing cellular degradation. L4-L6 from the spinal dorsal horns were isolated and harvested for studying protein expression, by the method of western blotting and immunofluorescence analysis. Results. The pain caused due to mechanical allodynia in the paw region was highest at 1 hour postinduction and lasted for three days postinjury. Pain was significantly less in the group receiving propofol when compared with the isoflurane group for the first two hours of injury. In the propofol group, EPAC1, GluN2B, and p38 MAP K were significantly lower. Conclusion. In the rat model of induced chronic contractile injury, postsurgery there was a suppression of the GluN2B-p38MAPK/EPAC1 signaling pathway in the propofol group. As the p38MAPK/EPAC pathway has a significant role in the postoperative hyperalgesia, thus our experiment suggests that propofol has analgesic effects.

scholarly journals Electroacupuncture Treatment Alleviates Central Poststroke Pain by Inhibiting Brain Neuronal Apoptosis and Aberrant Astrocyte Activation

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gui-Hua Tian ◽  
Shan-Shan Tao ◽  
Man-Tang Chen ◽  
Yu-Sang Li ◽  
You-Ping Li ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Signal Transmission ◽  
Low Frequency ◽  
Underlying Mechanism ◽  
Tunel Staining ◽  
Astrocyte Activation ◽  
Related Factors ◽  
Nissl Staining ◽  
Analgesic Effects ◽  
Cox 2

Electroacupuncture (EA) is reported to effectively relieve the central poststroke pain (CPSP). However, the underlying mechanism remains unclear. The present study investigated the detailed mechanisms of action of EA treatment at different frequencies for CPSP. A CPSP model was established with a single collagenase injection to the left ventral posterolateral nucleus of the thalamus. The EA-treated groups then received EA treatment at frequency of 2, 2/15, or 15 Hz for 30 min daily for five days. The pain-related behavioral responses, neuronal apoptosis, glial activation, and the expression of pain signal transmission-related factors (β-catenin, COX-2, and NK-1R) were assessed using behavioral tests, Nissl staining, TUNEL staining, and immunohistochemical staining, respectively. The low-frequency EA treatment significantly (1) reduced brain tissue damage and hematoma sizes and (2) inhibited neuronal apoptosis, thereby exerting abirritative effects. Meanwhile, the high-frequency EA treatment induced a greater inhibition of the aberrant astrocyte activation, accompanied by the downregulation of the expressions of COX-2,β-catenin, and subsequently NK-1R, thereby alleviating inflammation and producing strong analgesic effects. Together, these findings suggest that CPSP is closely related to pathological changes of the neocortex and hippocampus. EA treatments at different frequencies may exert abirritative effects by inhibiting brain neuronal apoptosis and aberrant astrocyte activation in the brain.

scholarly journals JAK2/STAT3 Signaling Pathway Plays a Key Role in Nicotine Mediated Neuroinflammation Suppression in an Ischemic Rat Model

2021 ◽  
Author(s):  
Qi Wang ◽  
Tingting Han ◽  
Ruihe Lai ◽  
Dalong Zhang ◽  
Yao Diao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Signaling Pathway ◽  
Rat Model ◽  
Inflammatory Factors ◽  
Spatial Learning And Memory ◽  
Sham Operation ◽  
Micropet Imaging ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Significant Difference

Abstract BackgroundTo explore the mechanism of nicotine mediated improvement of cognitive impairment in an established ischemic rat model. MethodsEndothelin-1 (ET-1) was injected into the left thalamic region in adult male Sprague-Dawley (SD) rats to establish ischemia model. 6 groups of rats (6 rats in each group) were then treated with nicotine, nicotine+DHβE, DHβE, AG490, nicotine +AG490 and saline respectively via intraperitoneal injection for 9 days. Another sham operation group was treated with saline as above. Morris Water Maze (MWM) test was performed for 6 consecutive days starting on the 4th day after operation to detect the cognitive function of rats in each group. 2-[18F]-A-85380 microPET imaging was performed on day 10 to evaluate the changes of α4β2 nAChRs in different brain regions of rats. Real-time PCR and Western blot were used to detect the amount of α4β2 nAChRs, JAK2, STAT3 and inflammatory factors in thalamus of rats in each group. ResultsThe results of MWM test showed the spatial learning and memory abilities of rats in the nicotine and sham operation groups were significantly better than the saline treating group in this ischemic rat model (p<0.05). There was no significant difference in other groups (p>0.05). MicroPET imaging showed more uptake of 2-[18F]-A-85380 in the nicotine, nicotine+AG490 and sham operation groups than in saline treating group, while there was no significant difference found in other groups (p>0.05). The expression of α4- and β2-nAChR in nicotine, nicotine+AG490 and sham operation groups was significantly higher than the saline treating group (p<0.05). In the nicotine group, the expression of p-JAK2 and p-STAT3 in left thalamus of rats was significantly higher than the saline treating group (p<0.05), and the expression of IL-1β and IL-6 protein was found to be lower than the saline treating group (p<0.05). While the expression of p-JAK2, p-STAT3 and inflammatory factors was not significantly different in all the other groups (p>0.05). ConclusionThe study suggests nicotine inhibits the expression of inflammatory factors by activating α4β2 nAChRs through the activation of JAK2-STAT3 signaling pathway to improve cognitive impairment in ischemic rats.

scholarly journals Acupuncture attenuates the development of diabetic peripheral neuralgia by regulating P2X4 expression and inflammation in rat spinal microglia

2020 ◽  
Vol 70 (1) ◽  
Author(s):  
He-yong Tang ◽  
Fan-jing Wang ◽  
Jun-long Ma ◽  
Hao Wang ◽  
Guo-ming Shen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Peripheral Neuropathy ◽  
Single Injection ◽  
Underlying Mechanism ◽  
Diabetic Rats ◽  
Inflammatory Factors ◽  
Once Daily ◽  
Withdrawal Threshold ◽  
Withdrawal Latency ◽  
Tnf Α

Abstract Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication of diabetes. The purpose of this study is to find the underlying mechanism for the effects of acupuncture in DPN rats. Rats were rendered diabetic with a single injection of 35 mg/kg streptozotocin (STZ). These STZ-diabetic rats were treated with acupuncture for 20 min once daily. The therapeutic efficacy of acupuncture was assessed using mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) evaluations. After 14 days treatment, acupuncture markedly reduced the pathological injury in STZ-diabetic rats. Moreover, it significantly down-regulated P2X4 and OX42 expression along with the reduced levels of inflammatory factors (CXCR3, TNF-α, IL-1β, IL-6), GSP and lipid metabolisms in the spinal cord of the DPN rats. Acupuncture could relieve DPN in rats by regulating P2X4 expression and inflammation in spinal microglia.

scholarly journals TLR4-MyD88-NF-κB signaling pathway contributes to the progression of secondary hepatic injury and fibrosis in hepatolithiasis

2021 ◽  
Vol 19 ◽  
pp. 205873922110147
Author(s):  
Yuan Fang ◽  
Lulu Zhou ◽  
Xiaoxuan Hu ◽  
Jingyun Guo ◽  
Jinmao Liao ◽  
...  
Keyword(s):  
Liver Function ◽  
Signaling Pathway ◽  
Hepatic Injury ◽  
Bile Duct Ligation ◽  
Inflammatory Factors ◽  
Pathological Changes ◽  
Duct Ligation ◽  
Tnf Α ◽  
Serum Biochemical ◽  
Liver Tissues

This paper focused on evaluating the effect of TLR4-MyD88-NF-κB signaling pathway in the progression of secondary hepatic injury and fibrosis in hepatolithiasis. The levels of inflammatory factors (IL-1β, IL-6, TNF-α) and serum biochemical values (ALT, AST, Tbil, Dbil, ALP, GGT) were detected by ELISA. IHC was used to detected the expression level of TLR4 in liver tissues of hepatolithiasis patients and mice. The pathological changes of liver tissue were observed by HE staining. The levels of MyD88, NF-κB, IκB, Laminin (LN), and chitosan enzyme 3-like protein 1 (CHI3L1) were detected by western blotting. In hepatolithiasis patients, the levels of TNF-α, IL-1β, and IL-6 were distinctly raised and proteins associated with TLR4-MyD88-NF-κB signaling pathway (such as TLR4, MyD88, NF-κB, and IκB) in liver tissues were significantly up-regulated. In Bile duct ligation (BDL) model of mice, the results showed that in addition to the significant increase of inflammatory factors, liver function indexes, and fibrosis indexes in BDL mice were also significantly up-regulated. Additionally, TLR4-MyD88-NF-κB signaling pathway was activated in BDL mice. After TLR4 knockdown in BDL mice, inflammatory factors, liver function indexes, and fibrosis indexes were significantly down-regulated. TLR4-MyD88-NF-κB signaling pathway proteins were restrained. TLR4-MyD88-NF-κB signaling pathway took part in the progression of secondary hepatic injury and fibrosis in hepatolithiasis. Inhibition of TLR4-MyD88-NF-κB signaling pathway can reduce the progression of secondary hepatic injury and fibrosis in hepatolithiasis.

scholarly journals Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Taemin Kim ◽  
Dong Rim Seol ◽  
Suk-Chan Hahm ◽  
Cheolwoong Ko ◽  
Eun-Hye Kim ◽  
...  
Keyword(s):  
Analgesic Effect ◽  
Weight Bearing ◽  
Temperature Sensitive ◽  
Therapeutic Tool ◽  
Withdrawal Threshold ◽  
Analgesic Effects ◽  
Joint Cavity ◽  
Monosodium Iodoacetate ◽  
The Right ◽  
Osteoarthritic Pain

The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 μL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 μL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 μL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 μL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 μL had a significant analgesic effect for 2 days, even though T-gel at 50 μL further reduced the weight load, demonstrating that intra-articular T-gel (20 μL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting.

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