The Modulatory Effect of Buprenorphine on Analgesia and Alteration in Expression of BDNF and CREB Genes in Rat Spinal Cord due to Intraperitoneal Injection of Methamphetamine

Abstract

Background: Methamphetamine is a commonly abused drug, and its neurotoxic effects have increased in recent years. There is growing evidence that buprenorphine, a widely used drug for pain management, reduces the harmful effects of addiction and is effective in treating opioid dependence. Objectives: This study aimed to investigate the interaction between methamphetamine and buprenorphine on analgesia and the expression of BDNF and CREB genes in the spinal cords of rats. Methods: In this study, 56 male Wistar rats (200 ± 50 g) were randomly assigned to eight groups: Control, sham, methamphetamine, two buprenorphine groups, two methamphetamine + buprenorphine groups, and a deprivation group. A one-way ANOVA test was used to analyze the data. Results: Intraperitoneal injection of methamphetamine (10 mg/kg) induced analgesia (P < 0.05) and increased CREB gene expression in the lumbar spinal cord (P < 0.01), whereas buprenorphine alone (6 and 10 mg/kg) did not induce significant analgesia or alter BDNF gene expression in the spinal cord. Pharmacological interactions revealed that buprenorphine (6 and 10 mg/kg, i.p.) enhanced the analgesic effect of methamphetamine. Additionally, while the lower dose of buprenorphine reduced methamphetamine's effect on CREB gene expression (P < 0.05), the higher dose potentiated the effect of methamphetamine on BDNF gene expression (P < 0.01) without significantly affecting CREB gene expression. Conclusions: The findings suggest that buprenorphine may enhance the analgesic effects of acute methamphetamine administration and modulate gene expression in the lumbar spinal cord of male Wistar rats.