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Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management
Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935995/ https://www.ncbi.nlm.nih.gov/pubmed/31921220 http://dx.doi.org/10.3389/fimmu.2019.03009 |
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author | Vanderwall, Arden G. Milligan, Erin D. |
author_facet | Vanderwall, Arden G. Milligan, Erin D. |
author_sort | Vanderwall, Arden G. |
collection | PubMed |
description | Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain management. In this review we first offer an overview of the relationships between pro-inflammatory cytokine and chemokine signaling and pathological pain, with a focus on the actions of cytokines and chemokines in communication between glia (astrocytes and microglia), immune cells (macrophages and T cells), and neurons. These interactions will be discussed in relation to both peripheral and central nervous system locations. Several novel non-neuronal drug targets for controlling pain are emerging as highly promising, including non-viral IL-10 gene therapy, which offer the potential for substantial pain relief through localized modulation of targeted cytokine pathways. Preclinical investigation of the mechanisms underlying the success of IL-10 gene therapy revealed the unexpected discovery of the powerful anti-nociceptive anti-inflammatory properties of D-mannose, an adjuvant in the non-viral gene therapeutic formulation. This review will include gene therapeutic approaches showing the most promise in controlling pro-inflammatory signaling via increased expression of anti-inflammatory cytokines like interleukin-10 (IL-10) or IL-4, or by directly limiting the bioavailability of specific pro-inflammatory cytokines, as with tumor necrosis factor (TNF) by the TNF soluble receptor (TNFSR). Approaches that increase endogenous anti-inflammatory signaling may offer additional opportunities for pain therapeutic development in patients not candidates for gene therapy. Promising novel avenues discussed here include the disruption of lymphocyte function-associated antigen (LFA-1) activity, antagonism at the cannabinoid 2 receptor (CB2R), and toll-like receptor 4 (TLR4) antagonism. Given the partial efficacy of current drugs, new strategies to manipulate neuroimmune and cytokine interactions hold considerable promise. |
format | Online Article Text |
id | pubmed-6935995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69359952020-01-09 Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management Vanderwall, Arden G. Milligan, Erin D. Front Immunol Immunology Current pain therapeutics offer inadequate relief to patients with chronic pain. A growing literature supports that pro-inflammatory cytokine signaling between immune, glial, and neural cells is integral to the development of pathological pain. Modulation of these communications may hold the key to improved pain management. In this review we first offer an overview of the relationships between pro-inflammatory cytokine and chemokine signaling and pathological pain, with a focus on the actions of cytokines and chemokines in communication between glia (astrocytes and microglia), immune cells (macrophages and T cells), and neurons. These interactions will be discussed in relation to both peripheral and central nervous system locations. Several novel non-neuronal drug targets for controlling pain are emerging as highly promising, including non-viral IL-10 gene therapy, which offer the potential for substantial pain relief through localized modulation of targeted cytokine pathways. Preclinical investigation of the mechanisms underlying the success of IL-10 gene therapy revealed the unexpected discovery of the powerful anti-nociceptive anti-inflammatory properties of D-mannose, an adjuvant in the non-viral gene therapeutic formulation. This review will include gene therapeutic approaches showing the most promise in controlling pro-inflammatory signaling via increased expression of anti-inflammatory cytokines like interleukin-10 (IL-10) or IL-4, or by directly limiting the bioavailability of specific pro-inflammatory cytokines, as with tumor necrosis factor (TNF) by the TNF soluble receptor (TNFSR). Approaches that increase endogenous anti-inflammatory signaling may offer additional opportunities for pain therapeutic development in patients not candidates for gene therapy. Promising novel avenues discussed here include the disruption of lymphocyte function-associated antigen (LFA-1) activity, antagonism at the cannabinoid 2 receptor (CB2R), and toll-like receptor 4 (TLR4) antagonism. Given the partial efficacy of current drugs, new strategies to manipulate neuroimmune and cytokine interactions hold considerable promise. Frontiers Media S.A. 2019-12-23 /pmc/articles/PMC6935995/ /pubmed/31921220 http://dx.doi.org/10.3389/fimmu.2019.03009 Text en Copyright © 2019 Vanderwall and Milligan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Vanderwall, Arden G. Milligan, Erin D. Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management |
title | Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management |
title_full | Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management |
title_fullStr | Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management |
title_full_unstemmed | Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management |
title_short | Cytokines in Pain: Harnessing Endogenous Anti-Inflammatory Signaling for Improved Pain Management |
title_sort | cytokines in pain: harnessing endogenous anti-inflammatory signaling for improved pain management |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935995/ https://www.ncbi.nlm.nih.gov/pubmed/31921220 http://dx.doi.org/10.3389/fimmu.2019.03009 |
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