New perspectives in our use of opioids

Some opioids in common use (eg, methadone) differ from others (eg, morphine) in beingN-methyl-d-aspartic acid receptor antagonists and inhibitors of monoamine transmitter reuptake. The nonopioid receptors mediating these effects have been shown to be involved in many pain states, and antagonists of these receptors act synergistically with mu opioid receptor agonists in promoting antinociception. This distinction emphasizes the need to reassess the basis of our use of opioids in the treatment of pain states that have previously been described as opioidinsensitive or opioid poorly responsive. In describing the activity of opioids, use of the term narrow spectrum or broad spectrum should reflect not only an assessment of actions mediated by opioid receptor classes (mu, delta, kappa, and subtypes), but also the actions mediated by nonopioid receptors. There are already indications that, in clinical situations, broad-spectrum opioids, such as methadone, are more effective than narrow spectrum opioids, such as morphine, in promoting pain relief in problematic situations such as neuropathic pain. Apart from this enlightenment in the treatment of pain, new opportunities for the use of opioids in the regulation of immune responses, and in the treatment of cancer disease, are also provided by the existence of opiate (morphine-related opioids)-specific binding sites in immunocytes and lung cancer cells. Further clinical trials with methadone, and more concerted laboratory work to identify other broad-spectrum opioids, and to characterize other nonopioid effects of opiates, are called for.