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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by
Jian Li1, Xiangnan Li2, Xin Jiang1
1Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
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.
Insights
Microglia-derived microvesicles exacerbate neuropathic pain by delivering interleukin-1β. Inhibiting this pathway and microvesicles shows therapeutic potential for pain management.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Microglia play a key role in neuropathic pain development.
- Microvesicles (MVs) are emerging mediators of intercellular communication.
- The specific role of microglial MVs in neuropathic pain remains unclear.
Purpose of the Study:
- To investigate the role of microvesicles (MVs) shed from microglia in the pathogenesis of neuropathic pain.
- To elucidate the molecular mechanisms underlying MV release and their effects on neuronal activity.
Main Methods:
- Induction of neuropathic pain via spinal nerve ligation (SNL) in a rat model.
- Quantification of microglial MVs in cerebrospinal fluid and spinal cord dorsal horn.
- Assessment of MVs' impact on pain behaviors (paw withdrawal threshold and latency).
- Analysis of the P2X7-p38 pathway and interleukin-1β (IL-1β) content within MVs.
- Electrophysiological recordings of synaptic currents following MV stimulation.
Main Results:
- SNL significantly increased microglial MVs in the cerebrospinal fluid and dorsal horn.
- Administered MVs reduced paw withdrawal threshold and latency, indicating increased pain sensitivity.
- The P2X7-p38 pathway was implicated in MV shedding post-SNL.
- Interleukin-1β was upregulated in MVs; its inhibition reversed pain hypersensitivity.
- MVs increased spontaneous excitatory postsynaptic currents, suggesting enhanced neuronal excitability.
Conclusions:
- Microglial MVs are significantly involved in neuropathic pain pathogenesis.
- The P2X7-p38 pathway regulates the shedding of MVs from microglia during neuropathic pain.
- MVs contribute to neuropathic pain by modulating microglia-neuron interactions, partly via IL-1β delivery.
