Chemokines and pain mechanisms

Catherine Abbadie, Sonia Bhangoo, Yves De Koninck, Marzia Malcangio, Stéphane Melik-Parsadaniantz, Fletcher White

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie the development of these chronic pain syndromes. It is now well established that astrocytic and microglial cells modulate the neuronal mechanisms of chronic pain in spinal cord and possibly in the brain. In animal models of neuropathic pain following peripheral nerve injury, several changes occur at the level of the first pain synapse between the central terminals of sensory neurons and second order neurons. These neuronal mechanisms can be modulated by pro-nociceptive mediators released by non neuronal cells such as microglia and astrocytes which become activated in the spinal cord following PNS injury. However, the signals that mediate the spread of nociceptive signaling from neurons to glial cells in the dorsal horn remain to be established. Herein we provide evidence for two emerging signaling pathways between injured sensory neurons and spinal microglia: chemotactic cytokine ligand 2 (CCL2)/CCR2 and cathepsin S/CX3CL1 (fractalkine)/CX3CR1. We discuss the plasticity of these two chemokine systems at the level of the dorsal root ganglia and spinal cord demonstrating that modulation of chemokines using selective antagonists decrease nociceptive behavior in rodent chronic pain models. Since up-regulation of chemokines and their receptors may be a mechanism that directly and/or indirectly contributes to the development and maintenance of chronic pain, these molecular molecules may represent novel targets for therapeutic intervention in sustained pain states.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalBrain Research Reviews
Volume60
Issue number1
DOIs
StatePublished - Apr 2009
Externally publishedYes

Fingerprint

Chemokines
Chronic Pain
Pain
Spinal Cord
cathepsin S
Microglia
Sensory Receptor Cells
Chemokine CX3CL1
Peripheral Nerve Injuries
Nociceptors
Chemokine Receptors
Spinal Ganglia
Neuralgia
Neuroglia
Astrocytes
Synapses
Rodentia
Up-Regulation
Therapeutics
Animal Models

Keywords

  • Cathepsin S
  • CCR2
  • CX3CR1
  • Fractalkine
  • MCP-1
  • Neuropathy
  • Pain

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Abbadie, C., Bhangoo, S., De Koninck, Y., Malcangio, M., Melik-Parsadaniantz, S., & White, F. (2009). Chemokines and pain mechanisms. Brain Research Reviews, 60(1), 125-134. https://doi.org/10.1016/j.brainresrev.2008.12.002

Chemokines and pain mechanisms. / Abbadie, Catherine; Bhangoo, Sonia; De Koninck, Yves; Malcangio, Marzia; Melik-Parsadaniantz, Stéphane; White, Fletcher.

In: Brain Research Reviews, Vol. 60, No. 1, 04.2009, p. 125-134.

Research output: Contribution to journalArticle

Abbadie, C, Bhangoo, S, De Koninck, Y, Malcangio, M, Melik-Parsadaniantz, S & White, F 2009, 'Chemokines and pain mechanisms', Brain Research Reviews, vol. 60, no. 1, pp. 125-134. https://doi.org/10.1016/j.brainresrev.2008.12.002
Abbadie C, Bhangoo S, De Koninck Y, Malcangio M, Melik-Parsadaniantz S, White F. Chemokines and pain mechanisms. Brain Research Reviews. 2009 Apr;60(1):125-134. https://doi.org/10.1016/j.brainresrev.2008.12.002
Abbadie, Catherine ; Bhangoo, Sonia ; De Koninck, Yves ; Malcangio, Marzia ; Melik-Parsadaniantz, Stéphane ; White, Fletcher. / Chemokines and pain mechanisms. In: Brain Research Reviews. 2009 ; Vol. 60, No. 1. pp. 125-134.
@article{2b82f6884de14089bfaf7474fcc618dd,
title = "Chemokines and pain mechanisms",
abstract = "The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie the development of these chronic pain syndromes. It is now well established that astrocytic and microglial cells modulate the neuronal mechanisms of chronic pain in spinal cord and possibly in the brain. In animal models of neuropathic pain following peripheral nerve injury, several changes occur at the level of the first pain synapse between the central terminals of sensory neurons and second order neurons. These neuronal mechanisms can be modulated by pro-nociceptive mediators released by non neuronal cells such as microglia and astrocytes which become activated in the spinal cord following PNS injury. However, the signals that mediate the spread of nociceptive signaling from neurons to glial cells in the dorsal horn remain to be established. Herein we provide evidence for two emerging signaling pathways between injured sensory neurons and spinal microglia: chemotactic cytokine ligand 2 (CCL2)/CCR2 and cathepsin S/CX3CL1 (fractalkine)/CX3CR1. We discuss the plasticity of these two chemokine systems at the level of the dorsal root ganglia and spinal cord demonstrating that modulation of chemokines using selective antagonists decrease nociceptive behavior in rodent chronic pain models. Since up-regulation of chemokines and their receptors may be a mechanism that directly and/or indirectly contributes to the development and maintenance of chronic pain, these molecular molecules may represent novel targets for therapeutic intervention in sustained pain states.",
keywords = "Cathepsin S, CCR2, CX3CR1, Fractalkine, MCP-1, Neuropathy, Pain",
author = "Catherine Abbadie and Sonia Bhangoo and {De Koninck}, Yves and Marzia Malcangio and St{\'e}phane Melik-Parsadaniantz and Fletcher White",
year = "2009",
month = "4",
doi = "10.1016/j.brainresrev.2008.12.002",
language = "English (US)",
volume = "60",
pages = "125--134",
journal = "Brain Research Reviews",
issn = "0165-0173",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Chemokines and pain mechanisms

AU - Abbadie, Catherine

AU - Bhangoo, Sonia

AU - De Koninck, Yves

AU - Malcangio, Marzia

AU - Melik-Parsadaniantz, Stéphane

AU - White, Fletcher

PY - 2009/4

Y1 - 2009/4

N2 - The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie the development of these chronic pain syndromes. It is now well established that astrocytic and microglial cells modulate the neuronal mechanisms of chronic pain in spinal cord and possibly in the brain. In animal models of neuropathic pain following peripheral nerve injury, several changes occur at the level of the first pain synapse between the central terminals of sensory neurons and second order neurons. These neuronal mechanisms can be modulated by pro-nociceptive mediators released by non neuronal cells such as microglia and astrocytes which become activated in the spinal cord following PNS injury. However, the signals that mediate the spread of nociceptive signaling from neurons to glial cells in the dorsal horn remain to be established. Herein we provide evidence for two emerging signaling pathways between injured sensory neurons and spinal microglia: chemotactic cytokine ligand 2 (CCL2)/CCR2 and cathepsin S/CX3CL1 (fractalkine)/CX3CR1. We discuss the plasticity of these two chemokine systems at the level of the dorsal root ganglia and spinal cord demonstrating that modulation of chemokines using selective antagonists decrease nociceptive behavior in rodent chronic pain models. Since up-regulation of chemokines and their receptors may be a mechanism that directly and/or indirectly contributes to the development and maintenance of chronic pain, these molecular molecules may represent novel targets for therapeutic intervention in sustained pain states.

AB - The development of new therapeutic approaches to the treatment of painful neuropathies requires a better understanding of the mechanisms that underlie the development of these chronic pain syndromes. It is now well established that astrocytic and microglial cells modulate the neuronal mechanisms of chronic pain in spinal cord and possibly in the brain. In animal models of neuropathic pain following peripheral nerve injury, several changes occur at the level of the first pain synapse between the central terminals of sensory neurons and second order neurons. These neuronal mechanisms can be modulated by pro-nociceptive mediators released by non neuronal cells such as microglia and astrocytes which become activated in the spinal cord following PNS injury. However, the signals that mediate the spread of nociceptive signaling from neurons to glial cells in the dorsal horn remain to be established. Herein we provide evidence for two emerging signaling pathways between injured sensory neurons and spinal microglia: chemotactic cytokine ligand 2 (CCL2)/CCR2 and cathepsin S/CX3CL1 (fractalkine)/CX3CR1. We discuss the plasticity of these two chemokine systems at the level of the dorsal root ganglia and spinal cord demonstrating that modulation of chemokines using selective antagonists decrease nociceptive behavior in rodent chronic pain models. Since up-regulation of chemokines and their receptors may be a mechanism that directly and/or indirectly contributes to the development and maintenance of chronic pain, these molecular molecules may represent novel targets for therapeutic intervention in sustained pain states.

KW - Cathepsin S

KW - CCR2

KW - CX3CR1

KW - Fractalkine

KW - MCP-1

KW - Neuropathy

KW - Pain

UR - http://www.scopus.com/inward/record.url?scp=63649140837&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63649140837&partnerID=8YFLogxK

U2 - 10.1016/j.brainresrev.2008.12.002

DO - 10.1016/j.brainresrev.2008.12.002

M3 - Article

C2 - 19146875

AN - SCOPUS:63649140837

VL - 60

SP - 125

EP - 134

JO - Brain Research Reviews

JF - Brain Research Reviews

SN - 0165-0173

IS - 1

ER -