Changes in the Gene Expression of β1 and β2 Integrins Following Development of Tolerance to Analgesic Effect of Morphine in Rats

Abstract

Objective: Considering the inhibitory effect of integrin-activity modulator (manganese) onthe development of morphine tolerance; in this study we have tried to assess the effectof chronic administration of both morphine and manganese on the expression levels of β1and β2 integrins in the dorsal horn of the lumbar spinal cord.Materials and Methods: Morphine tolerance was induced by intrathecal injection of morphine,15 μg/rat twice a day for five days. In order to study the effect of manganese on tolerancedevelopment; we injected manganese alone or in combination with morphine. Theanalgesic effect of morphine was assessed by using the tail flick test. Semi-quantitativereverse transcription - polymerase chain reaction (RT-PCR) was used to assess the expressionlevels of β1 and β2 integrins.Results: As assessed on day 6, five days administration of morphine significantly increasedthe expression levels of integrins β1 and β2. Combined administration of morphineand manganese, which inhibited morphine tolerance, prevented the effect of morphineon integrins’ expression.Conclusion: Increased expression of integrins may be due to direct effect of chronic morphineor a negative feedback that resulted from the potent inhibitory effect of morphine onintegrins’ activity. It seems that the activating of integrins via manganese in the presenceof morphine can reverse feedback and consequently the effect of chronic administrationof morphine on β1 and β2 integrins’ and expression. Our findings suggest a role for intracellularmatrix molecules in the development of morphine tolerance and possibly otherforms of synaptic plasticity.

Keywords

• Morphine
• Gene Expression
• Integrins
• Manganese
• Synaptic Plasticity