Effect of Umbelliprenin on Antinociceptive Activity of Morphine in a Rat Model of Neuropathic Pain Induced by Chronic Constriction Injury of the Sciatic Nerve

Objective: Although morphine is among the first-line medicines for the treatment of neuropathic pain, evidence has shown that the morphine efficacy gradually decreases and tolerance can occur. Regarding many reports concerning the antinociceptive and anti-inflammatory properties of umbelliprenin (UMB), this study aimed to investigate the effect of UMB on antinociceptive activity of morphine in a rat model of neuropathic pain induced by Chronic Constriction Injury (CCI) of the sciatic nerve. Methods: Twenty-four male Wistar rats were randomly divided into sham, CCI and CCI + UMB100 (100 mu g UMB per rat) groups. UMB was intrathecally administered once daily for four consecutive days (from the day before surgery until day 2 after surgery). All the animals received a single dose of morphine (5 mg/kg, s.c.) on day 14. To evaluate the effect of UMB on antinociceptive activity of morphine, allodynia and hyperalgesia were measured using the von-Frey and hot plate tests, before and 30 min after morphine injection and the Percentage of Maximum Possible Effect (%MPE) was calculated. Besides, the expression and concentration of tumor necrosis factor-alpha (TNF-alpha), as a proinflammatory cytokine, was measured in the spinal cord using quantitative real-time PCR (RTPCR) and ELISA, respectively. Results: UMB significantly enhanced anti-allodynic and anti-hyperalgesic effects of morphine in the neuropathic animals. Moreover, UMB considerably downregulated TNF-alpha expression in the spinal cord of the animals. Conclusion: UMB can enhance the antinociceptive effects of morphine, and this action may be partially due to its anti-inflammatory property.