Experimental Study Of The Relationships Between Nitric Oxide And Morphine Analgesia And Tolerance

Morphine is an opioid most frequently used for management of severe and chronic pain. The main disadvantage of morphine is the development of tolerance to analgesia which decreases its long-term effect of pain relief. A number of studies on tolerance to morphine analgesia have been done for the past few years. It is generally belived that the mechanisms underlying tolerance to morphine analgesia are highly complicated and involve many biological molecules and neuronal pathways, some of which still remain unclear. Nitric oxide (NO), a gaseous molecule, has increasingly become the interests of the biomedical researches. As an important chemical mediator and intracellular signaling molecule, NO plays a key modulatory role in numerous biological mechanisms. There have been several relevant studies attempting to clarify the interaction of NO and opioid receptors and the roles of NO in the nociceptive processes and, particularly in the actions of NO on morphine analgesia and tolerance, however, the no consistent results are achieved due to the differences in the experimental animal models, study methods and drug regimens. Accordingly, we carried out the present experiments, using both the formalin-induced inflammation and the thermal tail-flick rat models, to explore the effects of a single or chronic systemic administration of nitric oxide synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia and tolerance by measuring the expressions of c-fos gene, nNOSmRNA, NRlAmRNA, NR2AmRNA, and the extracellular concentrations of glutamate in spinal cord and midbrain, therey indentifing the relationship between NO and the mechanisms related to morphine analgesia and tolerance. The main purpose of our study is to further evaluate actions of NO on morphine analgesia and tolerance so as to provide a favorable inspiration for clinically dealing with tolerance to morphine analgesia.