The spinal action of Morphine may be explained by inhibition of the release of neurotransmitters from central terminals of C fibers and by a reduction in the excitability of post-synaptic dorsal horn neurons. These events imply the interruption of the nociceptive stimuli transmission through secondary neurons. However, the mechanisms underlying the analgesic effect of opioids of the new generation, which acts preferentially in peripheral tissues, are still not clarified. Experimental studies suggest that the antihyperalgesic action of opioids in peripheral tissue is mediated by reversion of the sensitization of primary afferent neurons, through inhibition of adenilciclase and activation of the L-argenine-NO-GMPc pathway that induces the opening of ATP-sensitive potassium-channels and consequently, hyperpolarization of primary afferent neurons. However, it has been demonstrated that membrane ATP-sensitive potassium-channels are expressed only in a small number of the primary nociceptive neurons, which does not explain the hyperpolarization of peripheral nociceptive fibers. It is known that the sensitization of primary sensory neurons is essential for inflammatory pain and that inflammation increases the density of opioid receptors in these fibers. Most of the studies about the mechanisms underlying analgesic effects of opioids demonstrate that they do not modify the nociceptive threshold, but blocked prostaglandin E2-induced inflammatory hyperalgesia. However, it was not demonstrated whether the increased opioid receptors expression in peripheral inflamed tissue is essential for the analgesic effectiveness of opioids. A previous study from our lab demonstrates that prostaglandin E2 significantly increases mu opioid receptor expression. In addition, we observe that peripheral morphine administration decreases the nociception induced by capsaicin, which stimulates only C fibers. Therefore, the aims of this work are,: (1) Verify whether peripheral administration of mu opioid receptor agonist inhibits C fibers stimulation; (2) Verify whether the antihyperalgesic action of the mu opioid receptor agonist depends on the prostaglandin E2; (3) Verify the contribution of the mitochondrial ATP-dependent potassium channels in these processes.
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