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

Objective: Considering the inhibitory effect of integrin-activity modulator (manganese) on the development of morphine tolerance; in this study we have tried to assess the effect of chronic administration of both morphine and manganese on the expression levels of beta(1) and beta(2) integrins in the dorsal horn of the lumbar spinal cord. Materials and Methods: Morphine tolerance was induced by intrathecal injection of morphine, 15 mu g/rat twice a day for five days. In order to study the effect of manganese on tolerance development; we injected manganese alone or in combination with morphine. The analgesic effect of morphine was assessed by using the tail flick test. Semi-quantitative reverse transcription - polymerase chain reaction (RT-PCR) was used to assess the expression levels of beta(1) and beta(2) integrins. Results: As assessed on day 6, five days administration of morphine significantly increased the expression levels of integrins beta(1) and beta(2). Combined administration of morphine and manganese, which inhibited morphine tolerance, prevented the effect of morphine on integrins' expression. Conclusion: Increased expression of integrins may be due to direct effect of chronic morphine or a negative feedback that resulted from the potent inhibitory effect of morphine on integrins' activity. It seems that the activating of integrins via manganese in the presence of morphine can reverse feedback and consequently the effect of chronic administration of morphine on beta(1) and beta(2) integrins' and expression. Our findings suggest a role for intracellular matrix molecules in the development of morphine tolerance and possibly other forms of synaptic plasticity.