Peripheral GABAA receptor-mediated signaling facilitates persistent inflammatory hypersensitivity
- Authors
- Lee, Pa Reum; Yoon, Seo-Yeon; Kim, Hyoung Woo; Yeo, Ji-Hee; Kim, Yong Ho; Oh, Seog Bae
- Issue Date
- Jun-2018
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Complete Freund' s adjuvant (CFA)-induced; persistent inflammatory hypersensitivity; GABA(A)R; Endogenous GABA; Picrotoxin; Bicuculline; 3 alpha,5 alpha-THP
- Citation
- NEUROPHARMACOLOGY, v.135, pp.572 - 580
- Journal Title
- NEUROPHARMACOLOGY
- Volume
- 135
- Start Page
- 572
- End Page
- 580
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3729
- DOI
- 10.1016/j.neuropharm.2018.04.009
- ISSN
- 0028-3908
- Abstract
- Unlike in the central nervous system (CNS), in the adult peripheral nervous system (PNS), activation of GABA(A) receptors (GABA(A)R) is excitatory because of the relatively high concentration of intracellular chloride in these neurons. Indeed, exogenous GABA and muscimol, a GABA(A)R agonist, exacerbate acute inflammatory hypersensitivity in rodents. However, it remains unclear whether peripheral GABA(A)R and the endogenous GABA play an important role in persistent inflammatory hypersensitivity. In this study, we thus investigated how peripheral GABA(A)R affects pain hypersensitivity by using the complete Freund's adjuvant (CFA)-induced persistent inflammatory pain mouse model. We found that intraplantar (i.pl.) administration of GABA(A)R antagonists, picrotoxin, and 1(S),9(R)-(-)-bicuculline methiodide significantly inhibited both spontaneous nociceptive (paw licking and flinching) behavior and mechanical hypersensitivity in CFA-injected mice at day 3 (D3), but not in naive mice. Interestingly, CFA induced mechanical hypersensitivity was significantly reversed by anti-GABA antibody (anti-GABA, i.pl.). In addition, RT-qPCR revealed that glutamate decarboxylase Gad] (GAD 67) and Gad2 (GAD 65) mRNA expression was also upregulated in the ipsilateral hind paw of CFA-injected mice at D3. Finally, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), a selective positive allosteric modulator of GABA(A)R, produced mechanical hypersensitivity in naive mice in a dose-dependent manner. Taken together, our results indicate that peripheral GABA(A)R and endogenous GABA, possibly produced by the inflamed tissue, potentiate CFA-induced persistent inflammatory hypersensitivity, suggesting that they can be used as a therapeutic target for alleviating inflammatory pain. (C) 2018 Elsevier Ltd. All rights reserved.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의예과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/3729)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.