Modulatory effect of the PDE-5 inhibitor sildenafil in diabetic neuropathy.

Abstract

Diabetic neuropathy is one of the most frequent peripheral neuropathies associated with hyperalgesia and hyperesthesia. Besides alteration in the levels of neurotransmitter, alteration in the neuronal nitric oxide synthase (nNOS) is a key factor in the pathogenesis of diabetic neuropathy. The present study was aimed at evaluating the role of PDE-5 inhibitor on nociception in streptozotocin-induced diabetes in animal models of nociception (writhing assay in mice and paw hyperalgesia test in rats). Diabetic animals showed a significant decrease in pain threshold as compared to non-diabetic animals in both tests, indicating diabetes induced hyperalgesia in mice and rats. The PDE-5 inhibitor, sildenafil, significantly increased the pain threshold in both diabetic and non-diabetic animals. However, L-NAME, a non-specific NOS inhibitor and methylene blue (MB), a guanylate cyclase inhibitor blocked the antinociceptive effect. The per se administration of L-NAME or MB augmented the hyperalgesic response in diabetic animals with little or no effect in non-diabetic animals, indicating the alteration of NO-cGMP pathway in diabetes. The results in the present study demonstrate that the decreased nNOS-cGMP system may play a crucial role in the pathogenesis of diabetic neuropathy.

• Authors: Chandrashekhar S Patil, Vijay Pal Singh, Sukhjeet Singh, Shrinivas K Kulkarni
• Journal: Pharmacology (Pharmacology) Vol. 72 Issue 3 Pg. 190-5 (Nov 2004) ISSN: 0031-7012 [Print] Switzerland
• PMID: 15452368 (Publication Type: Journal Article)

Chemical References

• Phosphodiesterase Inhibitors
• Piperazines
• Purines
• Sulfones
• Sildenafil Citrate
• 3',5'-Cyclic-GMP Phosphodiesterases
• Cyclic Nucleotide Phosphodiesterases, Type 5
• Pde5a protein, mouse
• Pde5a protein, rat
• Methylene Blue
• NG-Nitroarginine Methyl Ester

Topics

• 3',5'-Cyclic-GMP Phosphodiesterases (antagonists & inhibitors)
• Animals
• Cyclic Nucleotide Phosphodiesterases, Type 5
• Diabetes Mellitus, Experimental (complications, enzymology)
• Diabetic Neuropathies (complications, drug therapy, enzymology)
• Dose-Response Relationship, Drug
• Female
• Hyperalgesia (complications, drug therapy, enzymology)
• Male
• Methylene Blue (pharmacology)
• Mice
• NG-Nitroarginine Methyl Ester (pharmacology)
• Pain Threshold (drug effects)
• Phosphodiesterase Inhibitors (therapeutic use)
• Piperazines (therapeutic use)
• Purines
• Rats
• Rats, Wistar
• Sildenafil Citrate
• Sulfones