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Updated: May 29, 2026

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Induction of the P2X7 receptor in spinal microglia in a neuropathic pain model
Kimiko Kobayashi1, Emiko Takahashi, Yasuko Miyagawa
1Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Abstract:
Peripheral nerve injury causes a progressive series of morphological changes in spinal microglia, and extracellular ATP stimulates proliferation of microglia and may be involved in neuropathic pain. We defined the precise expression of P2X7 in the spinal cord following peripheral nerve injury. We found that both P2X7 mRNA and protein increased in the spinal cord, with a peak at 7d after injury. Double labeling studies revealed that cells expressing increased P2X7 mRNA and protein after nerve injury were predominantly microglia in dorsal horn. Pharmacological blockades by intrathecal administration of a P2X7 antagonist (A 438079 hydrochloride) suppressed the development of mechanical hypersensitivity. We present distinct evidence that increases in the number of P2X7 receptors in spinal microglia may play an important role in neuropathic pain.
Insights
Extracellular ATP and P2X7 receptors in spinal microglia contribute to neuropathic pain following peripheral nerve injury. Blocking P2X7 receptors reduced pain hypersensitivity, highlighting their role in pain development.
Area of Science:
- Neuroscience
- Pain Research
- Cell Biology
Background:
- Peripheral nerve injury induces changes in spinal microglia.
- Extracellular ATP is implicated in microglial proliferation and neuropathic pain.
Purpose of the Study:
- To investigate the expression of P2X7 receptors in the spinal cord after peripheral nerve injury.
- To determine the role of P2X7 receptors in the development of neuropathic pain.
Main Methods:
- Assessed P2X7 mRNA and protein expression in the spinal cord post-injury using molecular techniques.
- Utilized double labeling to identify cell types expressing P2X7.
- Administered a P2X7 antagonist (A 438079 hydrochloride) intrathecally.
- Evaluated the effect of antagonist on mechanical hypersensitivity.
Main Results:
- P2X7 mRNA and protein levels significantly increased in the spinal cord, peaking at 7 days post-injury.
- Upregulated P2X7 was predominantly found in microglia within the dorsal horn.
- Intrathecal administration of the P2X7 antagonist suppressed the development of mechanical hypersensitivity.
Conclusions:
- Increased P2X7 receptor expression in spinal microglia is a key feature following peripheral nerve injury.
- P2X7 receptors in spinal microglia play a significant role in the pathogenesis of neuropathic pain.
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