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The role of G‐protein‐coupled receptor kinase 2 in diabetic mechanical hyperalgesia in rats
Author(s) -
Xu XiuHua,
Du RuiQin,
Li Lin,
Yang LinLin,
Zhang Yi,
Li QuanMin
Publication year - 2021
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1819
Subject(s) - beta adrenergic receptor kinase , g protein coupled receptor kinase , dorsal root ganglion , receptor , chemistry , medicine , protein kinase a , adeno associated virus , kinase , pharmacology , endocrinology , g protein coupled receptor , biology , gene , spinal cord , recombinant dna , biochemistry , neuroscience , vector (molecular biology)
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.