Limits...
Systemic chemical desensitization of peptidergic sensory neurons with resiniferatoxin inhibits experimental periodontitis.

Breivik T, Gundersen Y, Gjermo P, Fristad I, Opstad PK - Open Dent J (2011)

Bottom Line: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays.LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone.The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway.

ABSTRACT

Background and objective: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected.

Material and methods: Resiniferatoxin (RTX; 50 μg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 μg/kg i.p.) to induce a robust immune and stress response.

Results: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone.

Conclusions: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways.

No MeSH data available.


Related in: MedlinePlus

A-B. Serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α  (A), and the anti-inflammatory cytokine interleukin (IL)-10 (B) 2 h after intraperitoneal injection of LPS (150 µg/kg) in resiniferatoxin-treated rats and vehicle-treated control rats. Resiniferatoxin-treated rats tended towards higher serum levels of TNF-α (p = 0.06), but lower IL-10 levels (* p < 0.001 vs. controls).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3040995&req=5

Figure 2: A-B. Serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α (A), and the anti-inflammatory cytokine interleukin (IL)-10 (B) 2 h after intraperitoneal injection of LPS (150 µg/kg) in resiniferatoxin-treated rats and vehicle-treated control rats. Resiniferatoxin-treated rats tended towards higher serum levels of TNF-α (p = 0.06), but lower IL-10 levels (* p < 0.001 vs. controls).

Mentions: After LPS challenge RTX-treated rats tended to react with higher TNF-α serum levels than vehicle-treated control rats (6052 ± 1307 ng/ml vs. 2934 ± 177 ng/ml; p = 0.055); (Fig. 2A). The serum levels of IL-10 were significantly lower in the RTX-treated rats compared with vehicle-treated controls.


Systemic chemical desensitization of peptidergic sensory neurons with resiniferatoxin inhibits experimental periodontitis.

Breivik T, Gundersen Y, Gjermo P, Fristad I, Opstad PK - Open Dent J (2011)

A-B. Serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α  (A), and the anti-inflammatory cytokine interleukin (IL)-10 (B) 2 h after intraperitoneal injection of LPS (150 µg/kg) in resiniferatoxin-treated rats and vehicle-treated control rats. Resiniferatoxin-treated rats tended towards higher serum levels of TNF-α (p = 0.06), but lower IL-10 levels (* p < 0.001 vs. controls).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3040995&req=5

Figure 2: A-B. Serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α (A), and the anti-inflammatory cytokine interleukin (IL)-10 (B) 2 h after intraperitoneal injection of LPS (150 µg/kg) in resiniferatoxin-treated rats and vehicle-treated control rats. Resiniferatoxin-treated rats tended towards higher serum levels of TNF-α (p = 0.06), but lower IL-10 levels (* p < 0.001 vs. controls).
Mentions: After LPS challenge RTX-treated rats tended to react with higher TNF-α serum levels than vehicle-treated control rats (6052 ± 1307 ng/ml vs. 2934 ± 177 ng/ml; p = 0.055); (Fig. 2A). The serum levels of IL-10 were significantly lower in the RTX-treated rats compared with vehicle-treated controls.

Bottom Line: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays.LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone.The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway.

ABSTRACT

Background and objective: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected.

Material and methods: Resiniferatoxin (RTX; 50 μg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 μg/kg i.p.) to induce a robust immune and stress response.

Results: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone.

Conclusions: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways.

No MeSH data available.


Related in: MedlinePlus