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Media type:
E-Article
Title:
Peripherally Acting Opioids and Clinical
Implications for Pain Control
Contributor:
Sehgal, Nalini
Published:
American Society of Interventional Pain Physicians, 2011
Published in:
Pain Physician, 3;14 (2011) 3;5, Seite 249-258
Language:
English
DOI:
10.36076/ppj.2011/14/249
ISSN:
2150-1149;
1533-3159
Origination:
Footnote:
Description:
Opioid receptors are widely expressed in the central and peripheral nervous systemand in the non-neuronal tissues. Data from animal and human clinical studies supportthe involvement of peripheral opioid receptors in analgesia, especially in the presenceof inflammation. Inflammation has been shown to increase the synthesis of opioidreceptors in the dorsal root ganglion neurons and enhance transport and accumulationof opioid receptors in the peripheral terminals of sensory neurons. Under the influenceof chemokines and adhesion molecules, opioid peptide-containing immune cellsextravasate and accumulate in the injured tissues.Stress, chemokines, cytokines, and other releasing factors in inflamed tissues stimulatethese granulocytes to release opioid peptides. Once secreted, opioid peptides bindto and activate peripheral opioid receptors on sensory nerve fibers and produceanalgesia by decreasing the excitability of sensory nerves and/or inhibiting release ofpro-inflammatory neuropeptides.Research has revealed that local application of exogenous opioid agonists produces apotent analgesic effect by activating peripheral opioid receptors in inflamed tissues.The analgesic activity occurs without activation of opioid receptors in the centralnervous system (CNS), and therefore centrally mediated side effects, such as respiratorydepression, mental clouding, altered consciousness, or addiction, are not associatedwith peripheral opioid activity. This discovery has stimulated research on developingperipherally restricted opioid agonists that lack CNS effects. In addition, it has beenrecognized that opioid receptors modulate inflammation, and that opioids have antiinflammatory effects. The anti-inflammatory actions of opioids are not well knownor understood. Conflicting reports on mu-opioids suggest both anti-inflammatoryand pro-inflammatory effects. This article will present the basis for peripheral opioidanalgesia and describe current research directed at developing novel treatments forpain with improved side effect profiles.Key words: Opioids, opioid receptors, opioid agonists, peripheral nervous system,peripheral opioid receptors