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Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons

Authors
 Hosung Jung  ;  Peter T. Toth  ;  Fletcher A. White  ;  Richard J. Miller 
Citation
 JOURNAL OF NEUROCHEMISTRY, Vol.104(1) : 254-263, 2008 
Journal Title
 JOURNAL OF NEUROCHEMISTRY 
ISSN
 0022-3042 
Issue Date
2008
Keywords
Chemokine ; Neurotransmitter ; DRG ; Neuropathic pain ; TRPV1 ; TRPA1
Abstract
It has previously been observed that expression of chemokine monocyte chemoattractant protein-1 (MCP-1/CC chemokine ligand 2 (CCL2)) and its receptor CC chemokine receptor 2 (CCR2) is up-regulated by dorsal root ganglion (DRG) neurons in association with rodent models of neuropathic pain. MCP-1 increases the excitability of nociceptive neurons after a peripheral nerve injury, while disruption of MCP-1/CCR2 signaling blocks the development of neuropathic pain, suggesting MCP-1 signaling is responsible for heightened pain sensitivity. To define the mechanisms of MCP-1 signaling in DRG, we studied intracellular processing, release, and receptor-mediated signaling of MCP-1 in DRG neurons. We found that in a focal demyelination model of neuropathic pain both MCP-1 and CCR2 were up-regulated by the same neurons including transient receptor potential vanilloid receptor subtype 1 (TRPV1) expressing nociceptors. MCP-1 expressed by DRG neurons was packaged into large dense-core vesicles whose release could be induced from the soma by depolarization in a Ca2+-dependent manner. Activation of CCR2 by MCP-1 could sensitize nociceptors via transactivation of transient receptor potential channels. Our results suggest that MCP-1 and CCR2, up-regulated by sensory neurons following peripheral nerve injury, might participate in neural signal processing which contributes to sustained excitability of primary afferent neurons.
Files in This Item:
T200895745.pdf Download
DOI
10.1111/j.1471-4159.2007.04969.x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
Jung, Ho Sung(정호성) ORCID logo https://orcid.org/0000-0002-5059-8050
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/108661
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