The mechanisms of microgliosis and pain following peripheral nerve injury

Calvo M.; Bennett, DLH

Keywords: microglia, neuropathic pain, Peripheral nerve injury

Abstract

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.

Más información

Título según WOS: The mechanisms of microgliosis and pain following peripheral nerve injury
Título de la Revista: EXPERIMENTAL NEUROLOGY
Volumen: 234
Número: 2
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2012
Página de inicio: 271
Página final: 282
Idioma: English
DOI:

10.1016/j.expneurol.2011.08.018

Notas: ISI