Spinal CX3CL1/CX3CR1 May Not Directly Participate in the Development of Morphine Tolerance in Rats

  • Yawen Peng
  • Genhua Guo
  • Bin Shu
  • Daiqiang Liu
  • Peng Su
  • Xuming Zhang
  • Feng Gao
Original Paper

Abstract

CX3CL1 (fractalkine), the sole member of chemokine CX3C family, is implicated in inflammatory and neuropathic pain via activating its receptor CX3CR1 on neural cells in spinal cord. However, it has not been fully elucidated whether CX3CL1 or CX3CR1 contributes to the development of morphine tolerance. In this study, we found that chronic morphine exposure did not alter the expressions of CX3CL1 and CX3CR1 in spinal cord. And neither exogenous CX3CL1 nor CX3CR1 inhibitor could affect the development of morphine tolerance. The cellular localizations of spinal CX3CL1 and CX3CR1 changed from neuron and microglia, respectively, to all the neural cells during the development of morphine tolerance. A microarray profiling revealed that 15 members of chemokine family excluding CX3CL1 and CX3CR1 were up-regulated in morphine-treated rats. Our study provides evidence that spinal CX3CL1 and CX3CR1 may not be involved in the development of morphine tolerance directly.

Keywords

Morphine tolerance Chemokine CX3CL1 CX3CR1 

Abbreviations

CCL2

C-C motif ligand 2

CCL5

C-C motif ligand 5

CCR1

C-C motif chemokine receptor 1

CXCL12

C-X-C motif ligand 12

CX3CL1

C-X3-C motif chemokine 1

CX3CR1

C-X3-C motif chemokine receptor 1

CXCR4

C-X-C motif chemokine receptor 4

rrCX3CL1

Recombinant rat CX3CL1 protein

DAMGO

[D-Ala2, N-MePhe4, Gly-ol]-enkephalin

DOR

delta opioid receptor

ERK

Extracellular regulated protein kinases

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GFAP

Glial fibrillary acidic protein

GLAST

Glutamate-aspartate transporters

GLT-1

Glutamate transporter-1

Iba-1

Ionized calcium-binding adapter molecule 1

IL-1β

Interleukin-1β

MPE

Maximal possible antinociceptive effect

MOR

Mu opioid receptor

NeuN

Neuronal nuclei

PAG

Periaqueductal gray

p38MAPK

p38 mitogen-activated protein kinase

PBS

Phosphate buffer saline

TNF-α

Tumor necrosis factor α

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yawen Peng
    • 1
  • Genhua Guo
    • 2
  • Bin Shu
    • 1
  • Daiqiang Liu
    • 1
  • Peng Su
    • 1
  • Xuming Zhang
    • 3
  • Feng Gao
    • 1
  1. 1.Department of Anesthesiology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science & TechnologyWuhanPeople’s Republic of China
  2. 2.Department of AnesthesiologyThe Central People’s Hospital of Ji’an CityJi’anPeople’s Republic of China
  3. 3.School of Life & Health SciencesAston UniversityBirminghamUK

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