Abstract
Vitexin, a C-glycosylated flavone present in several medicinal herbs, has showed various pharmacological activities including antinociception. The present study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain. This model was prepared by making a surgical incision on the right hindpaw and von Frey filament test was used to assess mechanical hyperalgesia. Isobolographical analysis method was used to examine the interaction between vitexin and acetaminophen. A reliable mechanical hyperalgesia was observed at 2 h post-surgery and lasted for 4 days. Acute vitexin administration (3–10 mg/kg, i.p.) dose-dependently relieved this hyperalgesia, which was also observed from 1 to 3 days post-surgery during repeated daily treatment. However, repeated vitexin administration prior to surgery had no preventive value. The 10 mg/kg vitexin-induced antinociception was blocked by the opioid receptor antagonist naltrexone or the GABAA receptor antagonist bicuculline. The doses of vitexin used did not significantly suppress the locomotor activity. In addition, the combination of vitexin and acetaminophen produced an infra-additive effect in postoperative pain. Together, though vitexin-acetaminophen combination may not be useful for treating postoperative pain, vitexin exerts behaviorally-specific antinociception against postoperative pain mediated through opioid receptors and GABAA receptors, suggesting that vitexin may be useful for the control of postoperative pain.
Highlights
Postoperative pain remains a major clinical problem after many surgeries
Repeated administration before surgery seems to have no preventive effect on postsurgical pain, the positive findings on antinociceptive effects produced by acute or repeated vitexin treatment suggest that vitexin may be useful as a new alterative agent for the management of postoperative pain
The antinociceptive effects of vitexin were able to be reversed by pretreatment with naltrexone or bicuculline, suggesting that both opioid receptors and GABAA receptors contribute to the antinociception of vitexin on postoperative pain
Summary
Postoperative pain remains a major clinical problem after many surgeries. The mismanagement of postoperative pain brings about a variety of negative consequences, such as chronic postsurgical pain and delayed rehabilitation[1]. Limited evidence from recent studies suggests that vitexin has pain-relieving abilities. Vitexin inhibits the pain-like behaviors and reduces the mechanical and thermal hyperalgesia in a variety of inflammatory pain mice models. The antinociceptive effects of vitexin against inflammatory pain may be partially mediated through targeting transient receptor potential vanilloid 1 (TRPV1) channel and oxidative stress and modulating cytokine production[28]. In order to provide further evidence for the clinical application of vitexin as an analgesic agent, this study investigated the antinociceptive effects of vitexin in a mouse model of postoperative pain and explored its potential pharmacological mechanisms. We examined the preventive effect of vitexin against postsurgical pain. It is well known that acetaminophen (paracetamol) is often used alone or in combination with traditional analgesics to treat postoperative pain; this study examined the interaction of vitexin combined with acetaminophen on postoperative pain
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