Title:Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain
Volume: 23
Issue: 26
Author(s): Katarzyna Popiolek-Barczyk and Joanna Mika
Affiliation:
Keywords:
Microglia, NF-κB, MAPK, ERK1/2, p38, STAT, PI3K/Akt, neuropathic pain.
Abstract: The microglia, once thought only to be supporting cells of the
central nervous system (CNS), are now recognized to play essential roles
in many pathologies. Many studies within the last decades indicated that
the neuro-immune interaction underlies the generation and maintenance of
neuropathic pain. Through a large number of receptors and signaling
pathways, the microglial cells communicate with neurons, astrocytes and
other cells, including those of the immune system. A disturbance or loss of
CNS homeostasis causes rapid responses of the microglia, which undergo
a multistage activation process. The activated microglia change their cell
shapes and gene expression profiles, which induce proliferation, migration,
and the production of pro- or antinociceptive factors. The cells release a large number
of mediators that can act in a manner detrimental or beneficial to the surrounding cells and
can indirectly alter the nociceptive signals. This review discusses the most important microglial
intracellular signaling cascades (MAPKs, NF-κB, JAK/STAT, PI3K/Akt) that are
essential for neuropathic pain development and maintenance. Our objective was to identify
new molecular targets that may result in the development of powerful tools to control the
signaling associated with neuropathic pain.
