Gabapentin regulates expression of FGF2 and FGFR1 in dorsal root ganglia via microRNA-15a in the arthritis rat model.

Abstract

Arthritis is an inflammatory disease with a prevalence rate of approximately 10% in China, which commonly manifests as pain. The aim of the current study was to investigate the function of gabapentin in the dorsal root ganglion in an arthritis rat model, and assess the effect of gabapentin on the expression of fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1). A total of 30 healthy male Sprague-Dawley rats were randomly divided into the following three groups: Untreated group, control group and gabapentin group. Rats in the control and the gabapentin groups were injected with Freund's complete adjuvant to induce arthritis. A total of 7 days subsequent to model establishment, the gabapentin group was administered intraperitoneally gabapentin for 8 days. The alterations in thickness of paw pad and paw withdrawal mechanical threshold (PWMT) were detected, which indicated that the rats in the control and gabapentin groups presented with the symptoms of arthritis. In the control group, the PWMT value was significantly reduced (P < 0.05), whereas the PWMT value was significantly increased in the gabapentin group. Immunohistochemistry demonstrated that the expression levels of FGF2 and FGFR1 were increased in the control group compared with the untreated group, while the expression levels of FGF2 and FGFR1 were reduced in the gabapentin group. Moreover, the FGF2 antagonist PD173074 partially improved the plantar thickness and PWMT of the arthritic rats. Bioinformatics analysis predicted microRNA-15a binding sites in the 3'untranslated regions (UTR) of FGF2 and FGFR1. Furthermore, the expression of microRNA-15a was reduced in the control group compared with untreated rats, whereas microRNA-15a in the gabapentin group was upregulated compared with the control. Additionally, the luciferase reporter assay confirmed that microRNA-15a could inhibit the protein expression through pairing with the 3'UTR of FGF2 and FGFR1 mRNAs. Gabapentin may relieve arthritis pain and reduce the expression of FGF2 and FGFR1 in dorsal root ganglia. Furthermore, microRNA-15a may be involved in the regulatory process.