Abstract
Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons.
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Abbreviations
- ANOVA:
-
Analysis of variance
- BCA:
-
Bicinchoninic acid
- CNS:
-
Central nervous system
- CSF:
-
Cerebrospinal fluid
- ELISA:
-
Enzyme-linked immunosorbent assay
- EM:
-
Electron microscopy
- MVs:
-
Microvesicles
- PBS:
-
Phosphate buffered saline
- PFA:
-
Paraformaldehyde
- PWT:
-
Paw withdrawal threshold
- PWL:
-
Paw withdrawal latency
- SEM:
-
Standard error
- SNL:
-
Spinal nerve ligation
- sEPSC:
-
Spontaneous excitatory postsynaptic currents.
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Acknowledgments
This work was funded by the National Natural Science Foundation of China (81371253), the Shanghai Municipal Education Commission (14ZZ083), and the Shanghai Changzheng Hospital (2015CZQN01).
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All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of the Second Military Medical University and conformed to the American Physiological Society’s Guiding Principles in the Care and Use of Animals.
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The authors declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.
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Jian Li, Xiangnan Li, and Xin Jiang contributed equally to this work and should be considered as co-first authors.
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Li, J., Li, X., Jiang, X. et al. Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats. Purinergic Signalling 13, 13–26 (2017). https://doi.org/10.1007/s11302-016-9537-0
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DOI: https://doi.org/10.1007/s11302-016-9537-0