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Changes in gene expression levels of the enzymes involved in biosynthesis and degradation of catecholamines following chronic administration of morphine and pain in rats

Introduction: Stress inhibits the development of tolerance to morphine analgesia via activating HypothalamicPituitary-Adrenal (HPA) axis. Modified catecholamine systems have been reported following morphine tolerance development. In the current study we tried to evaluate changes in the gene expression levels for MAO-A, MAO-B, COMT and thyrosine hydroxylase (TyH) enzymes following chronic pain, development of morphine tolerance and their combined administration. Methods: Analgesic tolerance was induced by intrapritoneal injections of morphine 20 mg/kg twice a day for 4 days. To study the effect of pain on morphine tolerance, 50 µl of formalin 5% was injected into the animal paws prior to morphine injections. Semi-quantitative RT-PCR was used to evaluate the gene expression level in lumbar spinal cord on day 5. Three separate control groups received saline or morphine injections or pain induction. Results: Chronic administration of morphine increased the expression level of MAO-B, decreased the expression of TyH and did not change the expression of COMT and MAO-A. Pain increased the expression of MAO-A, but did not change the expression of MAO-B, COMT and TyH. The combination of morphine treatment and pain induction for 4 days partially reversed the reduced expression of TyH and did not change the expression of MAO-A, MAO-B and COMT. Conclusion: Our results showed that in the context of morphine tolerance, gene expression was changed toward decreased biosynthesis and increased elimination of catecholamines. It seems that chronic administration of morphine caused lower level of catecholamines in spinal neurons and help development of morphine tolerance. Also, chronic pain partially produced compensational changes in gene expression. This may explain for its anti-tolerance effect.