| Scope and method of study. Opioids are the primary analgesic agents used for the treatment of severe pain. Opioid drugs mediate their effects through interaction with specific membrane bound receptor proteins. Opioid receptors reside on pain-processing neurons where their activation leads to an interruption of pain transmission. Unfortunately, opioids also exhibit profound adverse effects which are compounded by the development of tolerance to opioids. Moreover, opioids are addictive and are subsequently abused. Thus, much is still to be understood about these drugs in order to harness their powerful analgesic effects while omitting the unwanted side effects. Examination of drug receptor interaction as well as the intracellular mechanisms leading to these side effects will help facilitate a better understanding of opioid receptor pharmacology. Considering the obvious ethical issues associated with pain research, the ability to study opioid receptors in a lower vertebrate, if only for pilot studies to gain a better understanding of opioid action, would indeed be ideal. Several researchers have shown that an animal's ability to appreciate pain is highly correlated with vertebrate phylogenesis. The mechanisms of opioid ligands appear to be similar among vertebrates. These studies provide a systematic and ethically pleasing examination of opioid receptor pharmacology using a unique non-mammalian model employing complementary in vivo and in vitro techniques.; Findings and conclusions. These studies reveal that the same opioid agents that produce analgesia in humans elicit analgesia in amphibians with similar potencies. These studies comprehensively employed a well-established behavioral assay using selective antagonists to examine the properties of opioid receptors in the amphibian and indeed the results of these experiments allude to the working hypothesis which suggests the presence of a single type of opioid receptor (unireceptor) in the amphibian. Additionally, complementary radioligand binding studies using [3H]-naloxone in both amphibian brain and spinal cord tissue show nearly identical K i values for the three highly selective antagonists, beta-FNA (mu), nor-BNI (kappa) and NTI (delta). Together these behavioral and pharmacological data undeniably point to the mediation of antinociception in amphibians via interaction at a unique opioid receptor. |
