Control of Neuropathic Pain by Immune Cells and Opioids

Author(s): Halina Machelska.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 10 , Issue 5 , 2011

Abstract:

Neuropathic pain is a compilation of somatosensory, cognitive and emotional alterations developing following nerve injuries. Such pain often outlasts the initial cause and becomes a disease of its own that challenges its management. The actions of currently used anticonvulsants, antidepressants and opioids are hampered by serious central nervous system adverse effects, which preclude their sufficient dosing and long-term use. Conversely, selective activation of opioid receptors on peripheral sensory neurons has the advantage of pain relieve without central side effects. Considerable number of animal studies supports analgesic effects of exogenously applied opioids acting at peripheral opioid receptors in neuropathic conditions. In contrast to currently highlighted pain-promoting properties of neuroimmune interactions associated with neuropathy, recent findings suggest that opioid peptide-containing immune cells that accumulate at damaged nerves can also locally alleviate pain. Future aims include the exploration of opioid receptor signaling in injured nerves and of leukocytic opioid receptor function in pain modulation, development of approaches selectively delivering opioids and opioid-containing cells to injured tissues and investigation of interactions between exogenous and leukocyte-derived opioids. These efforts should lay a foundation for efficient and safe control of neuropathic pain. This article comprehensively analyzes the consequences of nerve injury on the expression of peripheral opioid receptors and peptides, and the impact of these changes on opioid analgesia, critically discussing positive and negative findings. Further focus is on a dual character of immune responses in the control of painful neuropathies.

Keywords: Analgesia, antinociception, inflammation, leukocytes, nerve injury, opioid peptides, opioid receptors, Dorsal Root Ganglia, CGRP, Axotomy, TRPV1, NRSF, POMC, PENK, SCID, NLX-M

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Article Details

VOLUME: 10
ISSUE: 5
Year: 2011
Page: [559 - 570]
Pages: 12
DOI: 10.2174/187152711796234952
Price: $58

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