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Updated: May 22, 2026
The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
The changes of mitochondrial cytochrome c and GABAergic neuron in neuropathic pain model
Won Sung Kim1, Ju Yeon Park, Tae Kyun Kim
1Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Busan, Korea.
Background:
Role of cytochrome c (Cyt c) is an apoptogenic agent under certain conditions. The mitochondrial permeability transition pore (MPTP) plays an important role in cell death since it opens, leading to mitochondrial swelling and release of Cyt c, which initiates apoptosis. By inhibiting the opening of MPTP, cyclosporine A (CSA) may contribute to maintaining mitochondrial homeostasis. We investigate the effects of the partial sciatic nerve injury (PSNI)-induced neuropathic pain model on mitochondrial Cyt c release and the effects of CSA on neuroprotection by mitochondrial stabilizing activity in PSNI rats.
Methods:
Rats were assigned to two groups that received different operations (Group P; PSNI operation, Group S; sham operation). The changes of cyt c and GABAergic neuron were evaluated in the spinal cord tissue. After which, PSNI rats randomly received CSA (Group C) or saline (Group S), and the changes of mechanical thresholds with Cyt c and GABAergic neuron were checked.
Results:
PSNI in rats increased the release of cytosolic Cyt c. However, GABAergic cells were not decreased in the spinal cord level on the ipsilateral side to the PSNI. The second experiment reveal a reduction in Cyt c release, using CSA in PSNI model. Rats receiving CSA were afforded the antiallodynia without decrease of GABAergic cell.
Conclusions:
The Cyt c probably contributes to nerve dysfunction after PSNI. PSNI induced neuropathic pain was profoundly linked to mitochondrial stabilization. Thus, the potent neuroprotector, CSA, might produce antiallodynia through its capability to inhibit the opening of MPTP.
Insights
Partial sciatic nerve injury (PSNI) causes neuropathic pain by increasing cytochrome c (Cyt c) release. Cyclosporine A (CSA) reduces this release and alleviates pain, suggesting Cyt c
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Cytochrome c (Cyt c) acts as an apoptogenic agent.
- Mitochondrial permeability transition pore (MPTP) opening leads to Cyt c release and apoptosis.
- Cyclosporine A (CSA) inhibits MPTP, potentially maintaining mitochondrial homeostasis.
Purpose of the Study:
- Investigate Cyt c release in a partial sciatic nerve injury (PSNI)-induced neuropathic pain model.
- Evaluate the neuroprotective effects of CSA in PSNI rats by stabilizing mitochondria.
Main Methods:
- Rats underwent either PSNI or sham operations.
- Spinal cord tissue was analyzed for Cyt c and GABAergic neuron changes.
- PSNI rats received CSA or saline, with subsequent assessment of mechanical thresholds, Cyt c, and GABAergic neurons.
Main Results:
- PSNI increased cytosolic Cyt c release without decreasing spinal cord GABAergic cells.
- CSA administration reduced Cyt c release in PSNI rats.
- CSA treatment resulted in antiallodynia without affecting GABAergic cell counts.
Conclusions:
- Cyt c release likely contributes to nerve dysfunction following PSNI.
- PSNI-induced neuropathic pain is strongly associated with mitochondrial instability.
- CSA demonstrates neuroprotective potential against neuropathic pain by inhibiting MPTP opening.
