VGLUT2/Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain by Complete Freund’s Adjuvant

Vesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in modulating release of glutamate, acted a key player in the formation of heat hyperalgesia of inflammatory pain. However, it remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in inflammatory pain mediated by Cdk5 in the inflammatory pain model induced by complete Freund’s adjuvant (CFA). Our results showed that the coexpression of Cdk5/VGLUT2 in small- and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA was significantly increased. Moreover, our study revealed that the expression of VGLUT2 protein in the DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection and was significantly reduced by roscovitine, a selective antagonist of Cdk5. Additionally, p25 but not p35, an activator of Cdk5, protein was significantly increased by CFA and reduced by roscovitine. Our findings suggested that VGLUT2/Cdk5 signaling pathway contributes to inflammatory pain mediated by Cdk5/p25.

Download Full-text

Role of Spinal Cord Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid Receptors in Complete Freund's Adjuvant-Induced Inflammatory Pain

Molecular Pain ◽

10.1186/1744-8069-4-67 ◽

2008 ◽

Vol 4 ◽

pp. 1744-8069-4-67 ◽

Cited By ~ 46

Author(s):

Jang-Su Park ◽

Myron Yaster ◽

Xiaowei Guan ◽

Ji-Tian Xu ◽

Ming-Hung Shih ◽

...

Keyword(s):

Spinal Cord ◽

Inflammatory Pain ◽

Complete Freund’S Adjuvant ◽

Freund’S Adjuvant ◽

Complete Freund's Adjuvant ◽

Freund's Adjuvant

Download Full-text

Trifluoro-Icaritin Ameliorates Complete Freund’s Adjuvant-Induced Inflammatory Pain by α7nAChR-Mediated Inhibition of HMGB1/NF-κB Signaling in the Spinal Cord of Rats

10.21203/rs.3.rs-572585/v1 ◽

2021 ◽

Author(s):

Yalan Sun ◽

Dandan Jia ◽

Meng Xue ◽

Guangsen Liu ◽

Zhihua Huang ◽

...

Keyword(s):

Spinal Cord ◽

Inflammatory Pain ◽

Intrathecal Injection ◽

Complete Freund’S Adjuvant ◽

Immunofluorescence Staining ◽

Western Blot Assay ◽

Freund’S Adjuvant ◽

Complete Freund's Adjuvant ◽

Freund's Adjuvant ◽

Alpha Bungarotoxin

Abstract Objectives: To explore whether Trifluoro-icaritin (ICTF) has anti-nociceptive effect on CFA-induced inflammatory pain and its potential mechanisms. Methods: Intraperitoneal injection (0.3, 1.0, and 3.0 mg/kg, i.p.) of ICTF to complete Freund’s adjuvant (CFA)-induced inflammatory pain rats once daily for 21 consecutive days. Pain-related behaviors were evaluated with paw withdrawal threshold (PWT), paw withdrawal latency (PWL), and CatWalk gait analysis. Hematoxylin eosin (HE) staining was applied to determine the morphological alterations in inflamed paw. Molecular docking was conducted to assess the possible targets for ICTF. Expression of pain-related signaling molecules in the spinal cord were detected using qRT-PCR, western blot assay, and immunoﬂuorescence staining. Results:This results showed that ICTF(3.0 mg/kg) effectively alleviated mechanical allodynia and thermal hyperalgesiabut not 0.3 and 1.0 mg/kg in CFA rats. Both paw edema volume and paw tissue inflammatory response were obviously reduced by ICTF. Subsequently, we further observed that ICTF dramatically decreased the mRNA and protein levels of HMGB1, NF-κB p65, and IL-1β but markedly enhanced α7nAChR and IL-10 expression in the spinal cord of CFA rats, and inhibitedthe co-expression of spinal α7nAChR with IBA-1 in double immunofluorescence staining,along with suppressing the alterations of gait parameters induced by CFA. Moreover, Intrathecal injection (i.t.) of α7nAChR antagonist alpha-bungarotoxin (α-Bgtx, 1.0 μg/kg) not only reversed the anti-nociceptive effect of ICTF on pain hypersensitivity, but also inhibited the down-regulation of HMGB1, NF-κB p65, and IL-1β as well as the up-regulation of α7nAChR and IL-10 protein expression induced by ICTF treatment.Conclusion: Our results illustrate that ICTF enables to alleviate CFA-induced inflammatory pain through α7nAChR-mediated inhibition of HMGB1/NF-κB signaling pathway in the spinal cord of rats, suggesting that ICTF may be exploited as a potential painkiller against chronic inflammatory pain.

Download Full-text

VGLUT2/ Cdk5/p25 Signaling Pathway Contributed to Inflammatory Pain By CFA

10.1101/655498 ◽

2019 ◽

Author(s):

YuWen Tang ◽

ZhiYou Peng ◽

ShouJun Tao ◽

Jianliang Sun ◽

WenYuan Wang ◽

...

Keyword(s):

Spinal Cord ◽

Signaling Pathway ◽

Inflammatory Pain ◽

Glutamate Transporter ◽

Underlying Mechanism ◽

Control Group ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase 5 ◽

Heat Hyperalgesia

AbstractVesicular glutamate transporter type 2 (VGLUT2) is known to play an important role in mediating the heat hyperalgesia induced by inflammation. However, the underlying mechanism for this activity is poorly understood. Cyclin-dependent kinase 5 (Cdk5), serving as a key regulator in mediating release of glutamate, contributed to the inflammatory heat. It remains unknown whether there is a bridge between Cdk5 and VGLUT2 for mediating inflammatory pain. Therefore, we designed the experiment to determine whether VGLUT2 signaling pathway is involved in Inflammatory pain mediated by Cdk5 and the heat hyperalgesia induced by complete Freund’s adjuvant (CFA) can be reversed by roscovitine, a selective inhibitor for Cdk5 through inhibition of VGLUT2 expression. Immunohistochemistry results suggest that when compared with rats in a control group, rats in an experimental group showed significant coexpression of Cdk5/VGLUT2 in small and medium-sized neuronal cells of the dorsal root ganglion (DRG) and spinal cord between days 1 and 3 following subcutaneous injection of CFA. Moreover, our study revealed that the expression of VGLUT2 protein in DRG and spinal cord was remarkably increased between days 1 and 3 following CFA injection. Additionally, p25 but not p35, a activator of Cdk5, protein was significantly increased and reduced by roscovitine. The increased expressions of VGLUT2 protein was significantly reduced by roscovitine as well. Our study showed that VGLUT2/Cdk5 signaling pathway contributed to the inflammatory pain medicated by Cdk5/p25.

Download Full-text