Fast Green FCF Alleviates Pain Hypersensitivity and Down-Regulates the Levels of Spinal P2X4 Expression and Pro-inflammatory Cytokines in a Rodent Inflammatory Pain Model

Abstract

Fast Green FCF (FGF), a biocompatible dye, recently drew attention as a potential drug to treat amyloid-deposit diseases due to its effects against amyloid fibrillogenesis in vitro and a high degree of safety. However, its role in inflammatory pain is unknown. Our study aimed to investigate the effect of FGF in the inflammatory pain model induced by complete Freund’s adjuvant (CFA) and to identify the associated mechanisms. We found that systemic administration of FGF reversed mechanical and thermal pain hypersensitivity evoked by CFA in a dose-dependent manner. FGF treatment decreased purinergic spinal P2X4 expression in the spinal cord of CFA-inflamed mice. FGF also down-regulated spinal and peripheral pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], but did not alter the spinal level of nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). In conclusion, our results suggest the potential of FGF for controlling the progress of inflammatory pain.

Fast Green FCF Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior and Downregulates TLR4/Myd88/NF-κB Signal Pathway in the Mouse Hippocampus

“…According to our previous study, we found that the anti-nociceptive effect of Fast green FCF was accumulative and a single Fast green FCF application did not reduce inflammatory pain. In addition, systemic administration of 100 mg/kg Fast green FCF had a more rapid and significant effect than 30 mg/kg Fast green FCF on inflammatory pain, and the anti-nociceptive effect of 100 mg/kg Fast green FCF persisted after the discontinuation of daily treatment (Xu et al, 2018). Therefore, we here investigated the anti-depressive effect of 100 mg/kg Fast green FCF administration (daily for 7 days, before LPS injection) on LPS-treated mice because LPS-induced depression-like behaviors occurred at 24 h after LPS treatment.…”

“…Our previous investigation suggests the relationship between Fast green FCF’s anti-nociceptive action and the downregulation of spinal P2X4R expression in CFA-induced inflammatory pain (Xu et al, 2018). Furthermore, some studies show that P2X4R is abundantly expressed in glial cells of the hippocampus and LPS facilitates P2X4R-mediated inward currents (Stokes et al, 2017).…”

“…The RT-PCR analysis was performed as previously described (Xu et al, 2018). Briefly, mice were anesthetized with CO2 and sacrificed 24 h after LPS treatment.…”

“…The molecular docking analysis was performed as previously described (Xu et al, 2018). Briefly, the analysis was performed by the SYBYL software (Tripos Inc., St. Louis, MO, United States) to predict the possible interaction between Fast green FCF and TLR4-MD2 complex.…”

“…Our previous study demonstrates that Fast green FCF could mitigate complete Freund’s adjuvant (CFA)-induced pain. The anti-nociceptive effect of Fast green FCF may involve downregulation of spinal purinergic P2X4 receptor (P2X4R), a key player in the development of chronic pain (Xu et al, 2018). However, it leaves questions open as to whether and how Fast green FCF affects inflammation-induced depressive symptoms.…”