<strong>The Multi-target Mechanism of CCL2/CCR2 Involved in Neuropathic Pain</strong>

Abstract

Abstract:CCL2 is the first discovered human CC chemokine and a potent chemotactic factor for monocytes，which induces immunological and inflammatory response. CCL2 and its receptor CCR2 play a key role in development and maintainence of neuropathic pain. Study found that CCL2 can be produced by neurons，and CCL2 acts as a neuromodulator in the process of pain disorder. CCL2 is the common mediator of neuropathic pain，immunological and inflammatory response. CCL2 involves in neuropathic pain at different levels，including peripheral sensory afferent nerve，dorsal root ganglia and spinal cord，which facilitates pain transmission. CCL2/CCR2 regulates neuropathic pain based on the following mechanisms：①enhances current amplitude and levels of TRPV1 mRNA by upregulating PI3K/Akt pathway，②CCL2 selectively increases mRNA of Nav1.8 through activating PI3K/Akt pathway and enhancing amplitude of TTX-R current，③significantly decreases voltage dependent noninactivation potassium current （IK） in DRG neurons，and has different effects on potassium channel in DRG neurons from different NP animal models，④enhances NMDA and AMPA evoked currents in spinal cord neurons，and enhances their spontaneous excitatory postsynaptic currents （EPSCs），⑤there is a bidirectional regulation between opioid receptors and CCL2/CCR2，⑥CCL2 directly inhibits GABA current in neurons.

Key words:monocyte chemoattractant protein-1（CCL2),C-C chemokine receptor type2(CCR2),neuropathic pain,ion channel,receptor

CLC Number:

R965

LI Li，ZHANG Hai-lin.The Multi-target Mechanism of CCL2/CCR2 Involved in Neuropathic Pain[J]. Acta Neuropharmacologica, 2016, 6(1): 49-57.

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The Multi-target Mechanism of CCL2/CCR2 Involved in Neuropathic Pain

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