Journal of Anesthesia

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

Opioids, gliosis and central immunomodulation

  • Salim Kadhim
  • John McDonald
  • David G. LambertEmail author
Invited Review Article


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.


Neuropathic pain Immunomodulation Glial cells Astrocytes Microglia Opioids Cytokines Gliosis 



Adenosine triphosphate


Blood–brain barrier


Brain-derived neurotrophic factor


Bromodeoxyuridine (5-bromo-2′-deoxyuridine)


Complement component 5a


Complement component 5a receptor


Chemokine (C-C motif) ligand 2


Chemokine (C-C motif) Receptor 2


C-C chemokine receptor type 3


Cluster of differentiation molecule 11B


Cluster of differentiation antigen 14


Central nervous system


Ciliary neurotrophic factor




Circumventricular organs


CX3C chemokine


CX3C chemokine receptor


Delta (\(\delta\)) opioid receptor


Similar to ErbB (avian erythroblastosis oncogene B)


Glial fibrillary acidic protein


Human immunodeficiency virus




International Association for the Study of Pain


Ionized calcium-binding adapter molecule 1














Inducible nitric oxide synthase


Integrin alpha M


Kappa (k) opioid receptor


Fifth Lumbar vertebra




Mitogen-activated protein kinase


Monocyte chemoattractant protein-1


Macrophage-colony stimulating factor


Macrophage-colony stimulating factor receptor


Mu (µ) opioid receptor


Nitric oxide


Nociceptin/orphanin FQ (N/OFQ) opioid receptor




Platelet P2Y12 receptor


Phospholipase A2


Regulated on activation, normal T cell expressed and secreted


Reactive oxygen species


Rostral ventromedial medulla


Transforming growth factor 1β


Toll-like receptor 4


Tumour necrosis factor alpha



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
    Email author
  1. 1.Department of Cardiovascular Sciences, Anaesthesia Critical Care and Pain ManagementUniversity of Leicester, Leicester Royal InfirmaryLeicesterUK

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