Korean J Anesthesiol.  2012 Apr;62(4):365-370. 10.4097/kjae.2012.62.4.365.

The changes of mitochondrial cytochrome c and GABAergic neuron in neuropathic pain model

• Kim WS
• Park JY
• Kim TK
• Baik SW

• KMID: 2238034
• DOI: http://doi.org/10.4097/kjae.2012.62.4.365

Abstract

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.

Keyword

Allodynia; Cyclosporine A; Cytochrome c; Mitochondrial permeability transition pore; Neuropathic pain

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Apoptosis
Cell Death
Cyclosporine
Cytochromes
Cytochromes c
Cytosol
GABAergic Neurons
Homeostasis
Hyperalgesia
Mitochondrial Membrane Transport Proteins
Mitochondrial Swelling
Neuralgia
Permeability
Rats
Salicylamides
Sciatic Nerve
Spinal Cord
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cyclosporine
Cytochromes
Cytochromes c
Mitochondrial Membrane Transport Proteins
Salicylamides