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Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis.

Zhao BS, Song XR, Hu PY, Meng LX, Tan YH, She YJ, Ding YY - PLoS ONE (2015)

Bottom Line: In addition, late HBO treatment reduced CCI-induced ultrastructural damage.HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms.Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.

ABSTRACT

Purpose: The aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlying mechanisms of HBO treatment.

Methods: Forty adult male Sprague-Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group. Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postoperative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemistry and western blot analysis. Cell apoptosis was measured using TUNEL staining. The expression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes.

Results: Early HBO treatment beginning on postoperative day 1 produced a persistent antinociceptive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postoperative day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apoptosis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatment beginning on postoperative day 6 produced a transient antinociceptive effect without changing the expression of P2X4R or CCI-induced apoptosis.

Conclusion: HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

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Related in: MedlinePlus

Electron micrographs showing the ultrastructure of spinal cord neurons in rats in the sham, CCI, HBO1, HBO2, and HBO3 groups.A. Representative electron micrographs showing the nucleus. Magnification: ×6000. B. Representative electron micrographs showing mitochondria (black arrows), rough endoplasmic reticulum (red arrows), and lysosomes (white arrows). Magnification: ×12,000.
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pone.0120122.g005: Electron micrographs showing the ultrastructure of spinal cord neurons in rats in the sham, CCI, HBO1, HBO2, and HBO3 groups.A. Representative electron micrographs showing the nucleus. Magnification: ×6000. B. Representative electron micrographs showing mitochondria (black arrows), rough endoplasmic reticulum (red arrows), and lysosomes (white arrows). Magnification: ×12,000.

Mentions: In the sham group, the neurons had round nuclei with a clear nuclear membrane and nucleoli. Chromatin was evenly distributed inside the nuclei (Fig. 5A). The cytoplasm was rich in ribosomes, rough endoplasmic reticulum, mitochondria, and Golgi complexes (Fig. 5B). In the CCI groups, the neurons had round nuclei with an unclear nuclear membrane. Ruptured cytoplasmic membranes and accumulated heterochromatin in the periphery were observed (Fig. 5A). The number of lysosomes in the cytoplasm was decreased, and the outer cristae of the mitochondria were unclear. An increase in the number of lysosomes, expansion of the endoplasmic reticulum, and swelling and vacuolation of mitochondria were noted(Fig. 5B). Early and middle HBO treatment did not reduce the CCI-induced ultrastructural damage. However, late HBO treatment reduced the CCI-induced damage, as indicated by the findings of a clear nuclear membrane (Fig. 5A), more ribosomes and rough endoplasmic reticulum, a clear outer membrane of the mitochondria, and fewer vacuolated mitochondria (Fig. 5B).


Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis.

Zhao BS, Song XR, Hu PY, Meng LX, Tan YH, She YJ, Ding YY - PLoS ONE (2015)

Electron micrographs showing the ultrastructure of spinal cord neurons in rats in the sham, CCI, HBO1, HBO2, and HBO3 groups.A. Representative electron micrographs showing the nucleus. Magnification: ×6000. B. Representative electron micrographs showing mitochondria (black arrows), rough endoplasmic reticulum (red arrows), and lysosomes (white arrows). Magnification: ×12,000.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4366063&req=5

pone.0120122.g005: Electron micrographs showing the ultrastructure of spinal cord neurons in rats in the sham, CCI, HBO1, HBO2, and HBO3 groups.A. Representative electron micrographs showing the nucleus. Magnification: ×6000. B. Representative electron micrographs showing mitochondria (black arrows), rough endoplasmic reticulum (red arrows), and lysosomes (white arrows). Magnification: ×12,000.
Mentions: In the sham group, the neurons had round nuclei with a clear nuclear membrane and nucleoli. Chromatin was evenly distributed inside the nuclei (Fig. 5A). The cytoplasm was rich in ribosomes, rough endoplasmic reticulum, mitochondria, and Golgi complexes (Fig. 5B). In the CCI groups, the neurons had round nuclei with an unclear nuclear membrane. Ruptured cytoplasmic membranes and accumulated heterochromatin in the periphery were observed (Fig. 5A). The number of lysosomes in the cytoplasm was decreased, and the outer cristae of the mitochondria were unclear. An increase in the number of lysosomes, expansion of the endoplasmic reticulum, and swelling and vacuolation of mitochondria were noted(Fig. 5B). Early and middle HBO treatment did not reduce the CCI-induced ultrastructural damage. However, late HBO treatment reduced the CCI-induced damage, as indicated by the findings of a clear nuclear membrane (Fig. 5A), more ribosomes and rough endoplasmic reticulum, a clear outer membrane of the mitochondria, and fewer vacuolated mitochondria (Fig. 5B).

Bottom Line: In addition, late HBO treatment reduced CCI-induced ultrastructural damage.HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms.Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, 510623, Guangzhou, China.

ABSTRACT

Purpose: The aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlying mechanisms of HBO treatment.

Methods: Forty adult male Sprague-Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group. Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postoperative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemistry and western blot analysis. Cell apoptosis was measured using TUNEL staining. The expression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes.

Results: Early HBO treatment beginning on postoperative day 1 produced a persistent antinociceptive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postoperative day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apoptosis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatment beginning on postoperative day 6 produced a transient antinociceptive effect without changing the expression of P2X4R or CCI-induced apoptosis.

Conclusion: HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

Show MeSH
Related in: MedlinePlus