Experimental neurology
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Experimental neurology · Apr 2012
ReviewThe mechanisms of microgliosis and pain following peripheral nerve injury.
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'. ⋯ 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.
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Experimental neurology · Apr 2012
ReviewMultiple mechanisms of microglia: a gatekeeper's contribution to pain states.
Microglia are gatekeepers in the CNS for a wide range of pathological stimuli and they blow the whistle when things go wrong. Collectively, microglia form a CNS tissue alarm system (Kreutzberg's "sensor of pathology"), and their involvement in physiological pain is in line with this function. ⋯ Such abnormal microglial behavior seems likely due to an as yet ill-understood disturbance of microglial functions unrelated to inflammation. The idea that microglia have roles in the CNS that differ from those of peripheral macrophages has gained momentum with the discovery of their separate, pre-hematopoietic lineage during embryonic development and their direct interactions with synapses.
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Experimental neurology · Apr 2012
ReviewSpatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats.
In the spinal cord, neuron and glial cells actively interact and contribute to neurofunction. Surprisingly, both cell types have similar receptors, transporters and ion channels and also produce similar neurotransmitters and cytokines. The neuroanatomical and neurochemical similarities work synergistically to maintain physiological homeostasis in the normal spinal cord. ⋯ In this review, we describe time and regional dependence of glial activation and describe activation mechanisms in various SCI models in rats. These data are placed in the broader context of glial activation mechanisms and chronic pain states. Our work in the context of work by others in SCI models demonstrates that dysfunctional glia, a condition called "gliopathy", is a key contributor in the underlying cellular mechanisms contributing to neuropathic pain.
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Experimental neurology · Apr 2012
ReviewATP receptors gate microglia signaling in neuropathic pain.
Microglia were described by Pio del Rio-Hortega (1932) as being the 'third element' distinct from neurons and astrocytes. Decades after this observation, the function and even the very existence of microglia as a distinct cell type were topics of intense debate and conjecture. However, considerable advances have been made towards understanding the neurobiology of microglia resulting in a radical shift in our view of them as being passive bystanders that have solely immune and supportive roles, to being active principal players that contribute to central nervous system pathologies caused by disease or following injury. ⋯ Microglia express several P2 receptor subtypes, and of these the P2X4, P2X7, and P2Y12 receptor subtypes have been implicated in neuropathic pain. The P2X4 receptor has emerged as the core microglia-neuron signaling pathway: activation of this receptor causes release of brain-derived neurotrophic factor (BDNF) which causes disinhibition of pain-transmission neurons in spinal lamina I. The present review highlights recent advances in understanding the signaling and regulation of P2 receptors expressed in microglia and the implications for microglia-neuron interactions for the management of neuropathic pain.