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Review ArticleReview Article

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

Christoph Stein and Halina Machelska
Burt M. Sharp, ASSOCIATE EDITOR
Pharmacological Reviews December 2011, 63 (4) 860-881; DOI: https://doi.org/10.1124/pr.110.003145
Christoph Stein
Department of Anesthesiology and Critical Care Medicine, Freie Universität Berlin, Charité Campus Benjamin Franklin, Berlin, Germany
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Halina Machelska
Department of Anesthesiology and Critical Care Medicine, Freie Universität Berlin, Charité Campus Benjamin Franklin, Berlin, Germany
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Burt M. Sharp
Department of Anesthesiology and Critical Care Medicine, Freie Universität Berlin, Charité Campus Benjamin Franklin, Berlin, Germany
Roles: ASSOCIATE EDITOR
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Abstract

The concept that the immune system can communicate with peripheral sensory neurons to modulate pain is based mostly on documented interactions between opioid ligands and receptors. Such findings may have broad implications for the development of safer pain medication. Innovative strategies take into account that analgesics should be particularly active in pathological states rather than producing a general suppression of the central nervous system, as with conventional morphine- or cannabinoid-like drugs. Inflammation of peripheral tissue leads to increased functionality of opioid receptors on peripheral sensory neurons and to local production of endogenous opioid peptides. In addition, endocannabinoids were detected in leukocytes, but their role in pain modulation has yet to be addressed. Future aims include the development of peripherally restricted opioid agonists, selective targeting of opioid-containing immune cells to sites of painful injury, and the augmentation of peripheral ligand and receptor synthesis (e.g., by gene therapy). Similar approaches may be pursued for cannabinoids. The ultimate goal is to avoid detrimental side effects of currently available analgesics such as respiratory depression, cognitive impairment, addiction, gastrointestinal bleeding, and thromboembolic complications.

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  • This article is available online at http://pharmrev.aspetjournals.org.

    doi:10.1124/pr.110.003145.

  • © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 63 (4)
Pharmacological Reviews
Vol. 63, Issue 4
1 Dec 2011
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Review ArticleReview Article

PERIPHERAL PAIN INHIBITION

Christoph Stein and Halina Machelska
Pharmacological Reviews December 1, 2011, 63 (4) 860-881; DOI: https://doi.org/10.1124/pr.110.003145

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Review ArticleReview Article

PERIPHERAL PAIN INHIBITION

Christoph Stein and Halina Machelska
Pharmacological Reviews December 1, 2011, 63 (4) 860-881; DOI: https://doi.org/10.1124/pr.110.003145
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  • Article
    • Abstract
    • I. Introduction
    • II. Opioids
    • III. Nonopioid Immune-Derived Modulators of Pain
    • IV. Therapeutic and Scientific Perspectives
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