Neurochemical Research

, Volume 42, Issue 11, pp 3254–3267 | Cite as

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 GaoEmail author
Original Paper


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.


Morphine tolerance Chemokine CX3CL1 CX3CR1 



C-C motif ligand 2


C-C motif ligand 5


C-C motif chemokine receptor 1


C-X-C motif ligand 12


C-X3-C motif chemokine 1


C-X3-C motif chemokine receptor 1


C-X-C motif chemokine receptor 4


Recombinant rat CX3CL1 protein


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


delta opioid receptor


Extracellular regulated protein kinases


Glyceraldehyde-3-phosphate dehydrogenase


Glial fibrillary acidic protein


Glutamate-aspartate transporters


Glutamate transporter-1


Ionized calcium-binding adapter molecule 1




Maximal possible antinociceptive effect


Mu opioid receptor


Neuronal nuclei


Periaqueductal gray


p38 mitogen-activated protein kinase


Phosphate buffer saline


Tumor necrosis factor α



Funding was provided by the National Natural Science Foundation of China (Nos. 81471143; 81171259).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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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
    Email author
  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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