Targeting Astrocyte Signaling for Chronic Pain

[문형철]

교세포(특히  microglia and astrocytes)와 만성통증과의 연관성에 관한 논문

argeting Astrocyte Signaling for Chronic Pain.pdf

서문. 

It has been increasingly recognized that glial cells, such as microglia and astrocytes in the central nervous system play an important role in the development and maintenance of chronic pain.

Notably, astrocytes make very close contacts with synapses and astrocyte reaction after nerve injury, arthritis, and tumor growth is more persistent than microglial reaction and displays a better correlation with chronic pain behaviors. 

Accumulating evidence indicates that activated astrocytes can release proinflammatory cytokines (e.g., IL-1β) and chemokines (e.g., MCP-1/CCL2) in the spinal cord to enhance and prolong persistent pain states. IL-1β can powerfully modulate

synaptic transmission in the spinal cord by enhancing excitatory synaptic transmission and suppressing inhibitory synaptic transmission. IL-1β activation (cleavage) in the spinal cord after nerve injury requires the matrix metalloprotease-2 (MMP-2). 

In particular, nerve injury and inflammation activate the c-Jun N-terminal kinase (JNK) in spinal astrocytes, leading to a substantial increase in the expression‎ and release of MCP-1. MCP-1 increases pain sensitivity via direct activation of NMDA receptors in dorsal horn neurons. 

Pharmacological inhibition of the IL-1β, JNK, MCP-1, or MMP-2 signaling via spinal administration has been shown to attenuate inflammatory, neuropathic, or cancer pain. Therefore, interventions in specific signaling pathways in astrocytes

may offer new approaches for the management of chronic pain.