Mortada, Y., Joharchi, K., Zarei, M., Mansouri, A., Jorjani, M. (2017). How Nitric Oxide increases in diabetic morphine tolerated male rats. Iranian Journal of Pharmaceutical Research, 16(2), 630-639. doi: 10.22037/ijpr.2017.2056
Mortada, Y., Joharchi, K., Zarei, M., Mansouri, A., Jorjani, M. (2017). 'How Nitric Oxide increases in diabetic morphine tolerated male rats', Iranian Journal of Pharmaceutical Research, 16(2), pp. 630-639. doi: 10.22037/ijpr.2017.2056
Mortada, Y., Joharchi, K., Zarei, M., Mansouri, A., Jorjani, M. How Nitric Oxide increases in diabetic morphine tolerated male rats. Iranian Journal of Pharmaceutical Research, 2017; 16(2): 630-639. doi: 10.22037/ijpr.2017.2056
How Nitric Oxide increases in diabetic morphine tolerated male rats
1Department of Pharmacology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2Shahid Beheshti University of Medical Sciences, Tehran, Iran
3Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract
Neuropathic pain is a complication of inflammation, infection or some diseases such as diabetes. Opioids are used as a salvage therapy for neuropathic pain but tolerance restricts their use. In our previous study we have observed an increase of Nitric Oxide in diabetes and in morphine tolerance. This study was performed to clarify the role of inducible nitric oxide synthase, iNOS, and cationic amino acid transporter, CAT-2, in these conditions. Thus male rats were divided into four groups: control, diabetic, morphine tolerated and diabetic morphine tolerated. For evaluating tolerance Hot-Plate test was achieved. Molecular study was performed by real time PCR and Western blotting techniques to compare gene and protein expression. Our findings showed that in diabetic animals, morphine tolerance occurred prior to non-diabetic rats. In molecular study, the expression of iNOS was increased in the spinal cord whereas the CAT-2 did not change in diabetic morphine tolerated rats. It seems that the nitric oxide elevation in diabetic morphine tolerated state is mostly due to the increase of iNOS in male rats.
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