The Role of Spinal PKCγ in Tolerance and Hyperalgesia Induced by Repeated Morphine Administration in Male Rats

Abstract

Background: The aim of this study was to investigate the possible role of Protein Kinase Cᵧ (PKCᵧ) in morphine tolerance and induced hyperalgesia following repeated morphine administration in male rats.  Material and Methods: Rats were divided into 4 groups for testing. The groups consisted of control (saline), morphine tolerance and hyperalgesia, metformine, morphine tolerance and hyperalgesia + metformine. First morphine (10mg/kg, s.c) administrated daily up to 14 days subcutaneously. Hargreaves' behavioral test was done before (control) and after the first dose of morphine on first day and then on day14th after last injection to evaluate morphine tolerance. To consider morphine hyperalgesia PWL was assessed by Hargreaves test before and after first morphine injection on first day and then on day 14th before last injection of morphine and on day16th two days after last injection of morphine. The expression of spinal PKCᵧ measured on day 14th and 16th. Metformin 100mg/kg, co-administrated with morphine daily up to 14 days then PWL and PKCᵧ expression were assessed as mentioned above. Results: The results showed significant tolerance and hyperalgesia on day 14th and 16th in compare to control. PKCᵧ expression also increased significantly on day 14th and 16th in compare to control but there was no significant differences in compare of day 14th and 16th. Co- administration of metformin and morphine up to 14 days increased PWL in morphine tolerance and reduced hyperalgesia and PKCᵧ expression. Conclusion: Results showed that increasing of spinal PKCᵧ expression in chronic morphine administration may involve in morphine tolerance and hyperalgesia.

Keywords

• morphine tolerance
• hyperalgesia
• metformin
• PkCγ