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Sensory Nerves pp 495-518 | Cite as

Opioids and Sensory Nerves

  • Christoph SteinEmail author
  • Christian Zöllner
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 194)

Abstract

This chapter reviews the expression and regulation of opioid receptors in sensory neurons and the interactions of these receptors with endogenous and exogenous opioid ligands. Inflammation of peripheral tissues leads to increased synthesis and axonal transport of opioid receptors in dorsal root ganglion neurons. This results in opioid receptor upregulation and enhanced G protein coupling at peripheral sensory nerve terminals. These events are dependent on neuronal electrical activity, and on production of proinflammatory cytokines and nerve growth factor within the inflamed tissue. Together with the disruption of the perineurial barrier, these factors lead to an enhanced analgesic efficacy of peripherally active opioids. The major local source of endogenous opioid ligands (e.g. β-endorphin) is leukocytes. These cells contain and upregulate signal-sequence-encoding messenger RNA of the β-endorphin precursor proopiomelanocortin and the entire enzymatic machinery necessary for its processing into the functionally active peptide. Opioid-containing immune cells extravasate using adhesion molecules and chemokines to accumulate in inflamed tissues. Upon stressful stimuli or in response to releasing agents such as corticotropin-releasing factor, cytokines, chemokines, and catecholamines, leukocytes secrete opioids. Depending on the cell type, this release is contingent on extracellular Ca2+ or on inositol triphosphate receptor triggered release of Ca2+ from endoplasmic reticulum. Once secreted, opioid peptides activate peripheral opioid receptors and produce analgesia by inhibiting the excitability of sensory nerves and/or the release of proinflammatory neuropeptides. These effects occur without central untoward side effects such as depression of breathing, clouding of consciousness, or addiction. Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing leukocytes to sites of painful injury, and the augmentation of peripheral opioid peptide and receptor synthesis.

Keywords

opioid peptides peripheral, opioid receptors immune cells peripheral analgesia immune cells inflammation pain cytokines chemokines secretory pathways G-protein coupled receptor signaling receptor recycling opioid tolerance endorphin enkephalin dynorphin endomorphin arthritis 

Notes

Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemein-schaft (KFO 100) and the International Anesthesia Research Society.

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© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Klinik für Anaesthesiologie und operative IntensivmedizinFreie Universität Berlin, Charité – Campus Benjamin FranklinBerlinGermany

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