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mGluR5 regulates inflammatory pain and pain aversion of CFA mice by mediating ERK/PI3K signaling pathway
Zhuang Tianxin1, Huang Zhongyu1, Zhang Weishan2
1School of Health, Guangdong Pharmaceutical University, Yunfun, China.
Abstract:
To investigate whether metabotropic glutamate receptor 5 (mGluR5) in the basolateral amygdala (BLA) regulates inflammatory pain and pain aversion by mediating ERK/PI3K signaling pathway in mice. Two experimental routes were designed. In route 1, 18 male C57BL/6 mice were divided into control, IFA, and CFA groups. In route 2, 18 mice received stereotaxic BLA injections of ACSF, the mGluR5 agonist DHPG, or antagonist MTEP on day 8 following CFA administration. Pain behaviors and aversive emotions were assessed over 14 days. BLA tissues were collected on day 15 for immunofluorescence staining and Western blot analyses of mGluR5, PI3K, p-PI3K, and ERK1/2 expression. The expression levels of p-PI3K, mGluR5 and ERK1/2 in the BLA of CFA mice were significantly increased, suggesting that their activation was associated with inflammatory pain. DHPG increased the expression of p-PI3K and mGluR5 and ERK1/2 in the CFA mouse brain BLA, while MTEP had the opposite effect. Our results show that mGluR5 regulates inflammatory pain and pain aversion of CFA mice by mediating the ERK/PI3K signaling pathway.
Insights
Metabotropic glutamate receptor 5 (mGluR5) in the basolateral amygdala (BLA) regulates inflammatory pain and aversion in mice. This regulation occurs via the ERK/PI3K signaling pathway, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Inflammatory pain and associated aversions are significant clinical concerns.
- The basolateral amygdala (BLA) plays a crucial role in processing pain and emotional responses.
- The involvement of metabotropic glutamate receptor 5 (mGluR5) in the BLA within inflammatory pain pathways requires further elucidation.
Purpose of the Study:
- To investigate the role of mGluR5 in the BLA in regulating inflammatory pain and pain aversion in a mouse model.
- To determine if the ERK/PI3K signaling pathway mediates the effects of mGluR5 in the BLA on pain behaviors.
Main Methods:
- Utilized a Complete Freund's Adjuvant (CFA)-induced inflammatory pain model in male C57BL/6 mice.
- Administered mGluR5 agonist (DHPG) or antagonist (MTEP) via stereotaxic BLA injections.
- Assessed pain behaviors and aversive emotions over 14 days.
- Analyzed BLA tissue using immunofluorescence and Western blot for mGluR5, PI3K, p-PI3K, and ERK1/2 expression.
Main Results:
- CFA administration significantly increased the expression of p-PI3K, mGluR5, and ERK1/2 in the BLA.
- Activation of mGluR5 with DHPG enhanced p-PI3K and ERK1/2 expression in the BLA of CFA mice.
- Antagonism of mGluR5 with MTEP reversed these expression changes.
Conclusions:
- mGluR5 in the BLA is critically involved in regulating inflammatory pain and pain aversion.
- The ERK/PI3K signaling pathway acts as a key mediator for mGluR5's effects on pain and aversion in the BLA.
- Targeting mGluR5 within the BLA may offer a novel therapeutic strategy for managing inflammatory pain and associated affective disorders.
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