scholarly journals Nav1.7 via Promotion of ERK in the Trigeminal Ganglion Plays an Important Role in the Induction of Pulpitis Inflammatory Pain

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Shukai Sun ◽  
Jiangxing Sun ◽  
Wenkai Jiang ◽  
Wei Wang ◽  
Longxing Ni
Keyword(s):  
Trigeminal Ganglion ◽  
Inflammatory Pain ◽  
Pain Threshold ◽  
Expression Levels ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Pulp Exposure ◽  
Mechanical Pain Threshold ◽  
Hematoxylin Eosin ◽  
Inhibitor Dose

The trigeminal ganglion (TG) refers to sensory neurons bodies that innervate the spinal cord and peripheral axons that innervate teeth. The tetrodotoxin-sensitive sodium (NA) channels (Nav1.7) play important roles in the pathophysiology of pain. In this study, we investigated the TG expression of Nav1.7 and extracellular signal-regulated kinase (ERK) in a rat model of pulpitis to explore the correlation between these channels and inflammatory pain. Pulpitis was confirmed by hematoxylin-eosin staining. In this study, we demonstrated that the reflex of rats to mechanical stimulation increases after pulp exposure and that the exposed rat molar pulp can upregulate the expression of Nav1.7 and ERK in the rat TG. Three days after rat pulp exposure, the expression levels of the two ion channels in the TG increased. TG target injection of PF04856264, a Nav1.7 inhibitor, dose-dependently increased the mechanical pain threshold and was able to inhibit ERK expression. TG target injection of PD98059, an ERK inhibitor, dose-dependently increased the mechanical pain threshold. These factors simultaneously resulted in the highest production. In this study, with the established link to inflammatory pain, we found that Nav1.7 and ERK both play important roles in the induction of inflammatory pain caused by pulpitis. We also found a correlation between the expression levels of Nav1.7 and ERK and the degree of inflammatory pain. Furthermore, ERK signaling pathways were promoted by the Nav1.7 in TG after pulpitis.

scholarly journals Analgesic Efficacy of a Combination of Fentanyl and a Japanese Herbal Medicine “Yokukansan” in Rats with Acute Inflammatory Pain

Medicines ◽  
2020 ◽  
Vol 7 (12) ◽  
pp. 75
Author(s):  
Yuko Akanuma ◽  
Mami Kato ◽  
Yasunori Takayama ◽  
Hideshi Ikemoto ◽  
Naoki Adachi ◽  
...  
Keyword(s):  
Inflammatory Pain ◽  
Late Phase ◽  
Analgesic Efficacy ◽  
Opioid Tolerance ◽  
High Dose ◽  
Erk Pathway ◽  
Single High Dose ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Combined Use

Background: Fentanyl can induce acute opioid tolerance and postoperative hyperalgesia when administered at a single high dose; thus, this study examined the analgesic efficacy of a combination of fentanyl and Yokukansan (YKS). Methods: Rats were divided into control, formalin-injected (FOR), YKS-treated+FOR (YKS), fentanyl-treated+FOR (FEN), and YKS+FEN+FOR (YKS+FEN) groups. Acute pain was induced via subcutaneous injection of formalin into the paw. The time engaged in pain-related behavior was measured. Results: In the early (0–10 min) and intermediate (10–20 min) phases, pain-related behavior in the YKS+FEN group was significantly inhibited compared with the FOR group. In the late phase (20–60 min), pain-related behavior in the FEN group was the longest and significantly increased compared with the YKS group. We explored the influence on the extracellular signal-regulated kinase (ERK) pathway in the spinal cord, and YKS suppressed the phosphorylated ERK expression, which may be related to the analgesic effect of YKS in the late phase. Conclusions: These findings suggest that YKS could reduce the use of fentanyl and combined use of YKS and fentanyl is considered clinically useful.

scholarly journals Extracellular Signal-Regulated Kinase Mediates Ebastine-Induced Human Follicle Dermal Papilla Cell Proliferation

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Fu-Ming Tsai ◽  
Chao-Hsu Li ◽  
Lu-Kai Wang ◽  
Mao-Liang Chen ◽  
Ming-Cheng Lee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Allergic Inflammation ◽  
Dermal Papilla ◽  
Dermal Papilla Cells ◽  
Expression Levels ◽  
Extracellular Signal Regulated Kinase ◽  
Hair Regrowth ◽  
Extracellular Signal ◽  
Elevated Expression ◽  
H1 Receptor Antagonist

Ebastine is a second-generation histamine H1 receptor antagonist that is used to attenuate allergic inflammation. Ebastine has also shown to affect hair loss; however, the immunoregulatory effect of ebastine cannot completely exclude the possibility of spontaneous hair regrowth in ebastine-treated mice. In this study, we examined the effects of ebastine on the growth of human follicle dermal papilla cells (HFDPC) using a WST-1 cell proliferation assay and a bromodeoxyuridine incorporation assay. Ebastine was shown to significantly increase the proliferation of HFDPC. The expression levels of cell-cycle regulatory proteins and an antiapoptotic protein were increased in ebastine-treated HFDPC. Furthermore, elevated expression levels of phospho-AKT and phospho-p44/42 extracellular signal-regulated kinase (ERK) were observed in ebastine-treated HFDPC. Ebastine-mediated HFDPC growth was completely reversed by blocking ERK kinase. The results from our present study suggest that the regulation of HFDPC proliferation by ebastine might be directly involved in hair regrowth through the ERK signaling pathway.

scholarly journals Inhibitory Effects of Palmatine on P2X7 Receptor Expression in Trigeminal Ganglion and Facial Pain in Trigeminal Neuralgia Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Cancan Yin ◽  
Wenhao Shen ◽  
Mingming Zhang ◽  
Lequan Wen ◽  
Ruoyu Huang ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Trigeminal Ganglion ◽  
P2x7 Receptor ◽  
Facial Pain ◽  
Pain Threshold ◽  
Receptor Expression ◽  
Infraorbital Nerve ◽  
Distribution Area ◽  
Tnf Α ◽  
Mechanical Pain Threshold

Trigeminal Neuralgia (TN) refers to recurrent severe paroxysmal pain in the distribution area of the trigeminal nerve, which seriously affects the quality of life of patients. This research applied the chronic constriction injury of the infraorbital nerve (CCI—ION) approach to induce an animal model of TN in rats. The mechanical pain threshold of each group of rats was determined postoperatively; the expression of P2X7 receptor in trigeminal ganglion (TG) was assessed by qRT-PCR, immunofluorescence and Western blot; and the changes of the proinflammatory cytokines IL-1β and TNF-α in serum of rats were detected by ELISA. The results showed that the administration of palmatine in the TN rats could reduce the mechanical pain threshold, significantly decrease the expression of P2X7 receptor in TG, and lower the serum concentrations of IL-1β and TNF-α, compared to the sham group. In addition, the phosphorylation level of p38 in TG of TN rats was significantly decreased after treatment with palmatine. Likewise, inhibition of P2X7 expression by shRNA treatment could effectively counteract the adversary changes of pain sensitivity, IL-1β and TNF-α production, and p38 phosphorylation in TN rats. Our data suggest that palmatine may alleviate mechanical facial pain in TN rats possibly by reducing the expression of P2X7 receptor in TG of TN rats, which may be attributable to inhibiting p38 phosphorylation and reducing the release of IL-1β and TNF-α.

Evaluation of the Expression Levels of Cannabinoid Type-1 (CB1) Receptor and Phosphorylated Extracellular Signal-Regulated Kinase (p-ERK) in Gliomas

2021 ◽  
Author(s):  
Nader Choucair ◽  
Zahraa Sakr ◽  
Hassane Kheir Eddine ◽  
Mariana Zaarour ◽  
Hayat Harati ◽  
...  
Keyword(s):  
Therapeutic Effects ◽  
Cb1 Receptors ◽  
Normal Brain ◽  
Clinicopathologic Features ◽  
Expression Levels ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Low Expression ◽  
Brain Tissues

Abstract Background Gliomas are the most frequent primary brain tumors and one of the most aggressive forms of cancer. Recently, numerous studies have focused on cannabinoids as a new cancer-therapeutic approach due to their antineoplastic effects through activation of the cannabinoid receptors, CB1 and CB2. The aim of this study was to investigate the expression levels of cannabinoid type-1 (CB1) receptors and phosphorylated extracellular signal-regulated kinase (p-ERK) in human glioma samples and evaluate their clinicopathologic significance. Materials and Methods We analyzed the expressions of CB1 receptors (CB1R) and p-ERK in 61 paraffin-embedded gliomas and 4 normal brain tissues using automated immunohistochemical assay. CB1R and p-ERK expressions were categorized into high versus low expression levels. Statistical analyses were performed to evaluate the association between CB1R and p-ERK expression levels and the clinicopathologic features and overall survival. Results Our results showed that CB1R is down-expressed in glioma tissues compared to normal brain tissues. However, the low expression of CB1R was found to be not related to the malignancy grade of gliomas. Conversely, higher expression of p-ERK was noted in gliomas compared to normal brain tissues, with no association observed with tumor grades. In addition, CB1R expression was not observed to be associated with clinicopathologic features of gliomas, except for p-ERK expression. Conclusion Our findings indicate a down-expression of CB1R and overexpression of p-ERK in glioma tissues when compared to non-cancerous brain tissues. This change in CB1R expression in gliomas may contribute to further research on the therapeutic effects of cannabinoids in human gliomas.

Osthole, a Coumadin Analog from Cnidium monnieri (L.) Cusson, Ameliorates Nucleus Pulposus-Induced Radicular Inflammatory Pain by Inhibiting the Activation of Extracellular Signal-Regulated Kinase in Rats

Pharmacology ◽  
2017 ◽  
Vol 100 (1-2) ◽  
pp. 74-82 ◽  
Author(s):  
Hai-Xuan Wu ◽  
Yi-Min Wang ◽  
Hui Xu ◽  
Ming Wei ◽  
Qiu-Lan He ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Nucleus Pulposus ◽  
Inflammatory Pain ◽  
Spinal Dorsal Horn ◽  
Lumbar Disc ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Spinal Dorsal ◽  
Extracellular Signal ◽  
Cox 2

Aim: This study was aimed at assessing the role of extracellular signal regulated kinase (ERK) in mechanical allodynia resulting from lumbar disc herniation (LDH) and exploring the osthole's anti-nociceptive effect on ERK activation. Methods: Radicular pain was generated by applying nucleus pulposus (NP) to the L5 dorsal root ganglion (DRG). Allodynia was measured using Von Frey filaments to calculate the mechanical pain threshold. Phosphorylated ERK and total ERK protein in the lumbar spinal dorsal horn was detected by using the Western blot technique. Cyclooxygenase 2 (COX-2) mRNA was assessed by real-time reverse-transcription polymerase chain reaction. Results: The application of NP to L5 DRG induced mechanical hypersensitivity which lasted for at least 28 days, and a significant increase of ERK phosphorylation in the ipsilateral spinal dorsal horn from postoperative day (POD) 1 to POD 21. ERK inhibitor attenuated NP-induced hyperalgesia compared to the dimethyl sulfoxide-(vehicle control) administered group (p < 0.05). Epidural treatment with osthole could ameliorate NP-evoked hyperalgesia by suppressing the activation of ERK rather than decreasing the expression of ERK protein. Osthole could also inhibit the increased expression of COX-2 mRNA in spinal dorsal horn, which was a known downstream effect of ERK signaling pathway. Conclusions: Our results suggest that ERK activation in the spinal dorsal horn plays a vital role in NP-evoked hyperalgesia. Osthole exerts analgesic effect on radicular inflammatory pain in LDH rat model, by down-regulating the mRNA expression of the target gene of COX-2 via inhibiting ERK activation in the spinal dorsal horn.

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