The role of G-protein-coupled receptor kinase 2 in diabetic mechanical hyperalgesia in rats.

Autor: Xu XH; Postgraduate Training Base of Jinzhou Medical University, The PLA Rocket Force characteristic Medical Center, Beijing, P. R. China., Du RQ; Department of Endocrinology, The PLA Rocket Forced Characteristic Medical Center, Beijing, P. R. China., Li L; Department of Endocrinology, The PLA Rocket Forced Characteristic Medical Center, Beijing, P. R. China., Yang LL; 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Zhang Y; Postgraduate Training Base of Jinzhou Medical University, The PLA Rocket Force characteristic Medical Center, Beijing, P. R. China., Li QM; Department of Endocrinology, The PLA Rocket Forced Characteristic Medical Center, Beijing, P. R. China.
Jazyk: angličtina
Zdroj: European journal of pain (London, England) [Eur J Pain] 2021 Oct; Vol. 25 (9), pp. 2039-2049. Date of Electronic Publication: 2021 Jul 03.
DOI: 10.1002/ejp.1819
Abstrakt: Background: Previous studies have indicated a negative correlation between GRK2 expression and pain development and transmission. Here, we investigated whether G-protein-coupled receptor kinase 2 (GRK2) was involved in regulating diabetic mechanical hyperalgesia (DMH).
Methods: The adeno-associated viral vectors containing the GRK2 gene (AAV-GRK2) were used to up-regulate GRK2 protein expression. The expression of GRK2 and exchange protein directly activated by cyclic adenosine monophosphate 1 (Epac1) in the dorsal root ganglion (DRG) of lumbar 4-6 was detected via immunoblotting and immunohistochemistry, and the transfection of the GRK2 gene was detected by immunofluorescence.
Results: Low levels of GRK2 were able to sustain STZ-induced pain in DMH rats. Intrathecal injection of AAV-GRK2 vector up-regulated GRK2 expression, providing pain rain to rats with DMH. With an increase in DMH duration, there was a decrease in paw withdrawal threshold (PWT) value, aggravating the pain, resulting in a decreasing pattern in GRK2 protein expression over time, whereas Epac1 protein expression showed an opposite trend.
Conclusion: GRK2 expression regulated DMH progression and is expected to play a role in the development of targeted therapy for DMH. GRK2 and Epac1 expressions play a vital role in maintaining pain in DMH rats.
(© 2021 European Pain Federation - EFIC®.)
Databáze: MEDLINE