Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn

Remifentanil-induced hyperalgesia (RIH) is known to be associated with oxidative stress and inflammation. Betulinic acid (BA) was reported to reduce visceral pain owing to its anti-oxidative and anti-inflammatory potential. Here, we ­explored whether BA can attenuate RIH through inhibiting oxidative stress and inflammation in spinal dorsal horn. Sprague-Dawley rats were randomly divided into 4 groups: Control, Incision, RIH, and RIH pre-treated with BA. After pretreated with BA (25 mg/kg, i.g.) for 7 days, rats were subcutaneo usly infused with remifentanil (40 μg/kg) for 30 min during right plantar incision surgery to induce RIH. The paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), spinal oxidative stress and inflammatory mediators were determined. Intraoperative remifentanil infusion i nduced postoperative hyperalgesia, as evidenced by the significant decrease in PWMT and PWTL (p #x3c; 0.01), and the significant increase in oxidative stress and inflammation evidenced by up-regulations of malondialdehyde, 3-nitrotyrosine, interleukin-1 β and tumour necrosis factor-α (p #x3c; 0.01) in spinal dorsal horn and matrix metalloproteinase-9 (MMP-9) activity (p #x3c; 0.01) in dorsal root ganglion, as well as a decrease in manganese superoxide ­dismutase activity (p #x3c; 0.01) compared with control and ­incision groups. All these results mentioned above were markedly reversed by pre-treatment with BA (p #x3c; 0.01) compared with RIH group. The...
Source: Pharmacology - Category: Drugs & Pharmacology Source Type: research