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Journal of Anesthesia

, Volume 32, Issue 5, pp 756–767 | Cite as

Opioids, gliosis and central immunomodulation

  • Salim Kadhim
  • John McDonald
  • David G. Lambert
Invited Review Article

Abstract

Neuropathic pain is a common health problem that affects millions of people worldwide. Despite being studied extensively, the cellular and molecular events underlying the central immunomodulation and the pathophysiology of neuropathic pain is still controversial. The idea that ‘glial cells are merely housekeepers’ is incorrect and with respect to initiation and maintenance of neuropathic pain, microglia and astrocytes have important roles to play. Glial cells differentially express opioid receptors and are thought to be functionally modulated by the activation of these receptors. In this review, we discuss evidence for glia-opioid modulation of pain by focusing on the pattern of astrocyte and microglial activation throughout the progress of nerve injury/neuropathic pain. Activation of astrocytes and microglia is a key step in central immunomodulation in terms of releasing pro-inflammatory markers and propagation of a ‘central immune response’. Inhibition of astrocytes before and after induction of neuropathic pain has been found to prevent and reverse neuropathic pain, respectively. Moreover, microglial inhibitors have been found to prevent (but not to reverse) neuropathic pain. As they are expressed by glia, opioid receptors are expected to have a role to play in neuropathic pain.

Keywords

Neuropathic pain Immunomodulation Glial cells Astrocytes Microglia Opioids Cytokines Gliosis 

Abbreviations

ATP

Adenosine triphosphate

BBB

Blood–brain barrier

BDNF

Brain-derived neurotrophic factor

BrdU

Bromodeoxyuridine (5-bromo-2′-deoxyuridine)

CC5a

Complement component 5a

CC5aR

Complement component 5a receptor

CCL2

Chemokine (C-C motif) ligand 2

CCR2

Chemokine (C-C motif) Receptor 2

CCR3

C-C chemokine receptor type 3

CD11B

Cluster of differentiation molecule 11B

CD14

Cluster of differentiation antigen 14

CNS

Central nervous system

CNTF

Ciliary neurotrophic factor

COX-2

Cyclooxygenase-2

CVO

Circumventricular organs

CX3CL1

CX3C chemokine

CX3CR1

CX3C chemokine receptor

DOP

Delta (\(\delta\)) opioid receptor

ErbB2

Similar to ErbB (avian erythroblastosis oncogene B)

GFAP

Glial fibrillary acidic protein

HIV

Human immunodeficiency virus

HPA

Hypothalamic–pituitary–adrenal

IASP

International Association for the Study of Pain

IBA1

Ionized calcium-binding adapter molecule 1

IFN-γ

Interferon-γ

IL-1

Interleukin-1

IL-13

Interleukin-13

IL-1β

Interleukin-1β

IL-4

Interleukin-4

IL-6

Interleukin-6

iNOS

Inducible nitric oxide synthase

ITGAM

Integrin alpha M

KOP

Kappa (k) opioid receptor

L5

Fifth Lumbar vertebra

LPS

Lipopolysaccharide

MAPK

Mitogen-activated protein kinase

MCP-1

Monocyte chemoattractant protein-1

M-CSF

Macrophage-colony stimulating factor

M-CSFR

Macrophage-colony stimulating factor receptor

MOP

Mu (µ) opioid receptor

NO

Nitric oxide

NOP

Nociceptin/orphanin FQ (N/OFQ) opioid receptor

NRG-1

Neuregulin1

P2Y12

Platelet P2Y12 receptor

PLA2

Phospholipase A2

RANTES

Regulated on activation, normal T cell expressed and secreted

ROS

Reactive oxygen species

RVM

Rostral ventromedial medulla

TGFβ

Transforming growth factor 1β

TLR-4

Toll-like receptor 4

TNF-α

Tumour necrosis factor alpha

Notes

Acknowledgements

SK is funded by a scholarship from Higher Committee for Education Development in Iraq.

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Copyright information

© Japanese Society of Anesthesiologists 2018

Authors and Affiliations

  • Salim Kadhim
    • 1
  • John McDonald
    • 1
  • David G. Lambert
    • 1
  1. 1.Department of Cardiovascular Sciences, Anaesthesia Critical Care and Pain ManagementUniversity of Leicester, Leicester Royal InfirmaryLeicesterUK

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