gardenoside and Neuralgia

Neuropathic pain is a severe health problem for which there is a lack of effective therapy. Ozone and Gardenia fruits have been used separately in pain relief for many years; however, their underlying mechanisms remain unclear. To investigate the pain‑relieving effects of combined ozone and Gardenia, a chronic constriction sciatic nerve injury (CCI) rat model was constructed and treated with ozone and gardenoside (Ozo&Gar), which is a compound found in Gardenia fruits. A total of 70 rats were randomly divided into five groups: Control (Ctrl), Ctrl + Ozo&Gar, Sham, CCI, and CCI + Ozo&Gar. The rats in the Ctrl + Ozo&Gar and CCI + Ozo&Gar groups were administered an intravenous injection of 30 µg/ml ozone and 300 µmol/l gardenoside. The rats in the Ctrl, Sham and CCI groups were administered the same volume of saline. Pain behavior, mechanical hyperalgesia, thermal hyperalgesia, and the protein expression levels of P2X3 and P2X7 purine receptors in L4‑L5 dorsal root ganglion (DRG) were determined 15 days post‑surgery. The results demonstrated that treatment with a combination of ozone and gardenoside increased mechanical withdrawal threshold and thermal withdrawal latency, thus confirming their pain‑relieving effects. In addition, a significant increase in the mRNA and protein expression levels of P2X3 and P2X7 was detected in the DRG of rats in the CCI group compared with in the control groups; however, following treatment with a combination of ozone and gardenoside, the mRNA and protein expression levels of P2X3 and P2X7 receptors were significantly reduced compared with in the CCI group. These results indicated that the mechanism underlying the pain‑relieving effects of ozone and gardenoside may be mediated by inhibition of P2X3 and P2X7 purine receptors in the DRG. This finding suggested that ozone and gardenoside may be considered potential drug candidates that target P2X3 and P2X7 purine receptors.

Topics: Animals; Gene Expression Regulation; Iridoids; Male; Neuralgia; Oxidants, Photochemical; Ozone; Pain Measurement; Peripheral Nerve Injuries; Rats; RNA, Messenger; Sciatic Neuropathy

Here, using rat model, we investigated the roles of gardenoside in the chronic constriction injury (CCI) of the ischiadic nerve.. Bennett and Xie's unilateral sciatic nerve CCI model was used in this study. A total of 60 rats were divided into control group (CN), sham group (Sham), CCI group, and gardenoside administrated CCI group. An aliquot of 5 mL gardenoside solution was administrated through gavage once per day for 14 d. Mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL) were detected. The levels of inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in spinal fluid were detected by ELISA. By using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, we analyzed the expression of P2X purinoceptor 3 and 7 (P2X3 and P2X7 receptors) in different groups. The expression of p-ERK/ERK and p-p38/p38 were also detected by western blot.. We found out that gardenoside could significantly improve the sciatica by partially restore the decrease of MWT and TWL in CCI rats. The levels of iNOS, IL-1β, and TNF-α were higher in CCI group (p < .05). The expressions of P2X3 and P2X7 were significantly increased in the CCI rats compared to control rats (p < .05). The levels of p-ERK/ERK and p-p38/p38 were also obviously increased in CCI group (p < .05). After treated with the gardenoside, these increases were decreased.. These results indicated that gardenoside may be able to relief CCI-induced neuropathic pain by regulating the P2X3 and the P2X7 expression on the ischiadic nerve.

Topics: Animals; Ganglia, Spinal; Gene Expression Regulation; Humans; Interleukin-1beta; Iridoids; Neuralgia; Nitric Oxide Synthase Type II; Pain Threshold; Rats; Receptors, Purinergic P2X3; Receptors, Purinergic P2X7; Sciatic Nerve; Tumor Necrosis Factor-alpha