Peripherally restricted opioid drugs: advances and retreats

The aim of this article is to familiarize anesthesiologists with recent research investigating peripheral opioid analgesia. The review focuses on studies of peripheral receptor distribution in humans and clinical data that support the hypothesis of peripheral analgesia that have been published over the past 2 years.

Recent anatomical studies using human tissue have detected the presence of mu-opioid receptors in epidermal and dermal layers of normal skin, although expression was not altered in certain dermal clinical conditions. Nerve fibers of human dental pulp also contained detectable mu-opioid receptors. A survey of the clinical literature on peripherally mediated mu analgesia suggests that under conditions of inflammation, the onset of analgesia is typically delayed, but once initiated, is of long duration. A peripherally selective kappa agonist was efficacious in relieving the pain associated with chronic pancreatitis.

Peripheral analgesia mediated through the mu-opioid receptor has been demonstrated in a variety of clinical settings, with the preponderance of data generated with arthroscopic procedures. Receptor localization studies using human tissue have corroborated the presence of the mu-opioid receptor in the periphery. Future research is needed to investigate the clinical utility of kappa and delta-opioid receptor agonists in the peripheral setting.