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1529239 
Journal Article 
The mechanisms of microgliosis and pain following peripheral nerve injury 
Calvo, M; Bennett, DLH 
2012 
Yes 
Experimental Neurology
ISSN: 0014-4886
EISSN: 1090-2430 
234 
2 
271-282 
21893056 
WOS:000301994900004 
Microglia are the resident macrophages in the central
nervous system (CNS). Any insult to the CNS homeostasis will induce a rapid change in microglia
morphology, gene expression profile and functional behaviour. These responses of microglia have
been collectively known as 'microgliosis'. Interestingly, damage to the nervous system outside
the CNS, such as axotomy of a peripheral nerve, can lead to microgliosis in the spinal cord.
There is a variation in the degree of microgliosis depending on the model of nerve injury
employed for instance this response is more marked following traumatic nerve injury than in
models of chemotherapy induced neuropathy. Following peripheral nerve injury nociceptive inputs
from sensory neurons appear to be critical in triggering the development of spinal microgliosis.
A number of signalling pathways including growth factors such as Neuregulin-1, matrix
metalloproteases such as MMP-9 and multiple chemokines enable direct communication between
injured primary afferents and microglia. In addition, we describe a group of mediators which
although not demonstrably shown to be released from neurons are known to modulate microglial
phenotype. There is a great functional diversity of the microglial response to peripheral nerve
injury which includes: Cellular migration, proliferation, cytokine release, phagocytosis, antigen
presentation and recruitment of T cells. It should also be noted that in certain contexts
microglia may have a role in the resolution of neuro-inflammation. Although there is still no
direct evidence demonstrating that spinal microglia have a role in neuropathic pain in humans,
these patients present a pro-inflammatory cytokine profile and it is a reasonable hypothesis that
these cells may contribute to this inflammatory response. Modulating microglial functions offers
a novel therapeutic opportunity following nerve injury which ideally would involve reducing the
pro-inflammatory nature of these cells whilst retaining their potential beneficial functions. (C)
2011 Elsevier Inc. All rights reserved. 
Microglia; Neuropathic pain; Peripheral nerve injury