Modulatory Effect of the PDE-5 Inhibitor Sildenafil in Diabetic Neuropathy

Vol. 72, No. 3, 2004

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Original Paper

Modulatory Effect of the PDE-5 Inhibitor Sildenafil in Diabetic Neuropathy
Chandrashekhar S. Patil^a, Vijay Pal Singh^a, Sukhjeet Singh^b, Shrinivas K. Kulkarni^a

^aPharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, and
^bPharmacology R&D, Panacea Biotec Ltd, Lalru, Punjab, India

Address of Corresponding Author

Pharmacology 2004;72:190-195 (DOI: 10.1159/000080104)

Key Words

Diabetic neuropathy
Hyperalgesia or hyperesthesia
PDE-5 inhibitors

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.

Author Contacts

Prof. S.K. Kulkarni
University Institute of Pharmaceutical Sciences
Panjab University
Chandigarh 160014 (India)
Tel. +91 172 534 113, Fax +91 172 541 409, E-Mail skpu@yahoo.com

Article Information

Received: February 2, 2004
Accepted after revision: April 13, 2004
Number of Print Pages : 6
Number of Figures : 6, Number of Tables : 0, Number of References : 30

Medline Abstract (ID 15452368)

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