Changes in beta 1 and beta 2 integrin genes expression in rat lumbar spinal cord is supportive of the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia

Introduction: In order to study the alterations of beta 1 and 2 integrins mRNA level in rat lumbar spinal cord following the induction of chronic pain and its effect on the development of tolerance to morphine analgesia, we examined the level of expression of these genes in the presence of chronic pain, which is an inhibitor of morphine tolerance. We used induction of chronic pain alone and in combination with morphine administration. Methods: In order to induce tolerance to analgesic effect of morphine, morphine (15 μg/rat) was intrathecally (i.t.) injected to male adult Wistar rats twice a day for 4 days. Chronic pain was induced using formalin %5, 15 minutes before morphine injections during days 1-4. The analgesic effect of morphine was measured using tail flick test. Lumbar spinal tissues were assayed for the expression of beta-1 and 2 integrins using ‘‘semi-quantitative RT-PCR’’ and were normalized to beta-actin. Results: Chronic administration of morphine for 4 days developed tolerance to morphine analgesia. Concomitant induction of pain with morphine administration inhibited the development of tolerance to the analgesic. Induction of chronic pain, 15 minutes before morphine injections resulted in significant increases in beta-1 and 2 integrins mRNA levels. Furthermore, chronic pain alone also resulted in increased beta-1 and 2 integrins mRNA. Conclusion: Our results showed that, the induction of chronic pain prior to morphine administration, which is able to prevent morphine tolerance, increases the expression of integrins. Chronic morphine administration resulted in increases of beta 1 and 2 integrins mRNA level in lumbar spinal cord. It may be suggested that increases of beta-1 and 2 integrins mRNA is the result of the negative feedback of integrin inhibition by chronic morphine administration. Chronic pain is an enhancer of beta-1 and 2 integrins and its simultaneous presence with morphine administration results in increased beta-1 and 2 integrins and as a result prevents the development of morphine tolerance.