&lt;p&gt;Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model&lt;/p&gt;

Chao, Yu–Faye; Li, Ping; Wang, Yanxiu; Zhang, Kaigang; Zheng, Zuncheng; Liang, Li‐Jung

doi:10.2147/dddt.s276424

Cited by 21 publications

(10 citation statements)

References 18 publications

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“… 31 , 58 Several studies have found that both sanguinarine and acupuncture attenuate neuropathic pain by inhibiting the p38 MAPK pathway. 59 , 60 Furthermore, TRPC6 may be implicated in inflammation via the p38 MAPK pathway. 61 , 62 In our study, we suggest that the analgesic effect of Dex was related to the inhibition of p38 phosphorylation and proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats

Xu¹,

Yi²,

Wang³

et al. 2022

JPR

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Purpose Neuropathic pain is a chronic intractable disease characterized by allodynia and hyperalgesia. Effective treatments are unavailable because of the complicated mechanisms of neuropathic pain. Transient receptor potential canonical 6 (TRPC6) is a nonselective calcium (Ca 2+ )-channel protein related to hyperalgesia. Dexmedetomidine (Dex) is an alpha-2 (α2) adrenoreceptor agonist that mediates intracellular Ca 2+ levels to alleviate pain. However, the relationship between TRPC6 and Dex is currently unclear. We speculated that the α2 receptor agonist would be closely linked to the TRPC6 channel. We aimed to investigate whether Dex relieves neuropathic pain by the TRPC6 pathway in the dorsal root ganglia (DRG). Methods The chronic constriction injury (CCI) model was established in male rats, and we evaluated the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The expression of TRPC6 and Iba-1 in the DRG were analyzed using quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence assay. The levels of inflammatory cytokines were measured using an enzyme-linked immunosorbent assay. Results Compared with the CCI normal saline group, both the MWT and TWL were significantly improved after 7 days of Dex administration. Results demonstrated that TRPC6 expression was increased in the DRG following CCI but was suppressed by Dex. In addition, multiple administrations of Dex inhibited the phosphorylation level of p38 mitogen-activated protein kinase and the upregulation of neuroinflammatory factors. Conclusion The results of this study demonstrated that Dex exhibits anti-nociceptive and anti-inflammatory properties in a neuropathic pain model. Moreover, our findings of the CCI model suggested that Dex has an inhibitory effect on TRPC6 expression in the DRG by decreasing the phosphorylation level of p38 in the DRG.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats

Xu¹,

Yi²,

Wang³

et al. 2022

JPR

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“…ROS could act as beneficial molecules to adjust intracellular physiology and trigger cytotoxicity relying on their concentration and duration. The superoxide production triggered by the compounds induced p38 MAPK signaling pathway lead to PARP cleavage, caspases [25–27] . Moreover, MAPKs and PI3K/Akt pathway interacted with several points of cross‐talk and feedback loops [28] .…”

Section: Methodsmentioning

confidence: 99%

Cytotoxic Activity, Apoptosis Induction and Structure–Activity Relationship of 2‐Phenylphthalazin‐2‐ium Salts as Promising Antitumor Agents

et al. 2022

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Inspired by sanguinarine and chelerythrine, various 2‐phenylphthalazin‐2‐ium salts as simple analogues were designed according to the structure of natural products. On the basis of previous research, this study evaluated the inhibition activity of these compounds on tumor cells, apoptosis induction as well as their structure‐activity relationship (SAR). The results indicated that the compounds showed IC50 values of 1.21–14.77 μM against NB4 cells and 4.68–17.44 μM against MKN‐45 cells, respectively, superior to positive control cis‐platinum with IC50 values of 2.39 and 11.36 μM or their model compound chelerythrine with IC50 values of 1.49 and 12.70 μM. Acridine orange/ethidium bromide and ultrastructure observation of cells suggested that these compounds could induce apoptosis of tumor cells. Meanwhile, 2‐(3,4‐Dichlorophenyl)phthalazin‐2‐ium Bromide‐induced apoptosis was dependent on the excessive formation of ROS and amplified by the mitochondrial pathway. The preliminary SAR indicated that substitution pattern on the N‐aromatic ring remarkably influenced the cytotoxicity of the compounds. The trend showed that the presence of electron‐donating groups caused a significant improvement of the cytotoxicity. And in many cases that the 3’ site was the most advantageous substitution position for the enhancement of the cytotoxicity. Hence, the results demonstrated that the title compounds werea class of potential compounds for the development of novel antitumor drugs.

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“…After sealing with tri-buffered saline Tween-20 (TBST) containing 5% skimmed milk for 1 h at room temperature, the membrane was incubated with diluted anti-rabbit antibodies against NPY (#11,976, 1:1000; Cell signaling technology, Danvers, MA, USA), NPY1R (ab91262,1:1000; Abcam), NPY2R (PA5-77,517, 1:200; Thermo Fisher Scientific), p38 MAPK (#8690, 1:2000, Cell Signaling Technology), ERK (#4370, 1:2000, Abcam) and GAPDH (ab9485, 1:5000; Abcam; internal inference) at 4°C overnight. Next, the membrane was incubated with horseradish peroxidase-labeled secondary antibody goat anti-rabbit against IgG (S0001, Affinity BioReagents Inc., Golden, Colorado, USA) for 1 h. The enhanced chemiluminescence kit (BB-3501, Amersham, Arlington Heights, IL, USA) was used for visualization of bands, which were quantified in the gel imager [ 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

Neuropeptide Y in the amygdala contributes to neuropathic pain-like behaviors in ratsviathe neuropeptide Y receptor type 2/mitogen-activated protein kinase axis

Yan

Liu

et al. 2022

Bioengineered

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Neuropeptide Y (NPY) is a highly conserved endogenous peptide in the central and peripheral nervous systems, which has been implicated in nociceptive signaling in neuropathic pain. However, downstream mechanistic actions remain uncharacterized. In this study, we sought to investigate the mechanism of NPY and its receptor NPY2R in the amygdala in rats with neuropathic pain-like behaviors induced by chronic constriction injury (CCI) of the sciatic nerve. The expression of NPY and NPY2R was found to be aberrantly up-regulated in neuropathic pain-related microarray dataset. Further, NPY was found to act on NPY2R in the basolateral amygdala (BLA). As reflected by the decrease in mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) as well as the increase of NPY expression in the amygdala of rats with neuropathic pain-like behaviors, NPY was closely related to the effect of amygdala nerve activity in neuropathic pain. Subsequently, mechanistic investigations indicated that NPY2R activated the MAPK signaling pathway in the amygdala. NPY2R-induced decrease of MWT and TWL were also restored in the presence of MAPK signaling pathway antagonist. Moreover, it was revealed that NPY2R overexpression promoted the viability while inhibiting the apoptosis of microglia. Taken together, NPY in the amygdala interacts with NPY2R to activate the MAPK signaling pathway, thereby promoting the occurrence of neuropathic pain.

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<p>Sanguinarine Attenuates Neuropathic Pain by Inhibiting P38 MAPK Activated Neuroinflammation in Rat Model</p>

Cited by 21 publications

References 18 publications

Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats

Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats

Cytotoxic Activity, Apoptosis Induction and Structure–Activity Relationship of 2‐Phenylphthalazin‐2‐ium Salts as Promising Antitumor Agents

Neuropeptide Y in the amygdala contributes to neuropathic pain-like behaviors in ratsviathe neuropeptide Y receptor type 2/mitogen-activated protein kinase axis

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