How Nitric Oxide Increases in Diabetic Morphine Tolerated Male Rats

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-2, 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 expressions. 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.