Peripheral opioid analgesia: from experimental to clinical studies

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Abstract
Previous experimental findings demonstrating that the local administration of opioids produces dose-dependent and naloxone-reversible analgesic effects, which are restricted to the periphery, have now been confirmed in clinical studies. Accordingly, opioid receptors have been identified on peripheral sensory neurons of animals and humans. In addition to their efficacy in somatic pain, peripheral opioids potently inhibit visceral pain. These effects are enhanced under inflammatory conditions. Initial clinical trials have now examined local opioid effects in chronic inflammatory states such as arthritis. They demonstrated surprisingly long-lasting analgesic effects, probably caused by additional anti-inflammatory effects. The introduction of a new generation of opioids that act selectively in the periphery may open a novel approach to treating pain effectively without undesirable central side-effects such as respiratory depression and addiction.