Abstract
Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. Effective treatment for neuropathic pain is still lacking, due in part to poor understanding of pathological mechanisms at the molecular level. Neuronal mechanisms of neuropathic pain, especially synaptic plasticity, are the major focus of many investigators. N-methyl-D-aspartate (NMDA) receptor dependent synaptic plasticity at the spinal and cortical levels is believed to contribute to enhanced sensory responses after injury. Glial cells, including astrocytes and microglia, have recently been implicated in neuropathic pain. These glial cells form close interactions with neurons and thus may modulate nociceptive transmission under pathological conditions. In this review, we present recent progress in the study of neuronal and microglial mechanisms underlying neuropathic pain. We propose that activity-dependent neuronal plasticity is a key target for treatment in neuropathic pain.
Highlights
Pain is an unpleasant sensory experience induced by noxious stimuli
We have confirmed the activation of spinal microglial cells after nerve injury, we did not find any microgliosis in supraspinal structures, including the somatosensory cortex and the anterior cingulate cortex (ACC) (Figure 3)
NMDA receptors play important roles in various cognitive functions, while microglia survey the microenvironment in the brain
Summary
Pain is an unpleasant sensory experience induced by noxious stimuli. Physiological pain is important for animals to avoid potential injury, while pathological pain is unpleasant, lasts for an extended period of time after injury and is characterized by a heightened responsiveness to both noxious and non-noxious stimuli (hyperalgesia and allodynia, respectively). We have confirmed the activation of spinal microglial cells after nerve injury, we did not find any microgliosis in supraspinal structures, including the somatosensory cortex and the ACC (Figure 3) These findings are consistent with our recent study demonstrating that microglial motility was not altered by neuronal activity or LTP induction in the aforementioned brain regions [62]. In spite of this lack of microgliosis, we cannot completely exclude the possibility that microglia are altered at the biochemical and molecular levels in neuropathic pain. Microglia respond to several neuronal-derived signals which may lead to microglial activation after peripheral nerve injury These signaling pathways include ATP and its receptors (P2X and P2Y receptor), fractalkine and CX3CR1, monocyte chemotactic protein (MCP-1) and CCR2.
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