Neuropeptides and Microglial Activation in Inflammation, Pain, and Neurodegenerative Diseases

Figure 1

Neuropeptide modulation of microglial activation. In the presence of noxious stimuli such as LPS, Aβ, and IFN-γ or in the context of neuroinflammation or tissue damage, microglial cells produce a plethora of inflammatory mediators that promote and perpetuate the inflammatory response, potentially leading to neurodegeneration. Neuropeptides, acting through specific receptors present in microglial cells, are able to modulate microglial response and inhibit the release of inflammatory mediators while favoring development of an alternative activation program. On the other hand, neuropeptides such as SP, β-END, and leptin exert proinflammatory actions on microglial cells and may even potentiate the response to noxious stimuli. In experimental models of pain, certain neuropeptides such as SP, CGRP, and AM have been suggested to increase pain hypersensitivity partly by promoting proinflammatory activation of spinal cord microglia.