Differential effect of spironolactone in chronic constriction injury and vincristine-induced neuropathic pain in rats.

Abstract

The present study was designed to investigate the ameliorative potential of spironolactone in chronic constriction injury and vincristine-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, while vincristine (50 μg/kg) was administered for 10 days to induce chemotherapy-induced neuropathic pain. Acetone drop, pin-prick, hot plate and paint brush tests were performed to assess cold allodynia; mechanical and heat hyperalgesia; dynamic mechanical allodynia, respectively. The spontaneous pain and postural index in terms of foot deformity was also assessed. The levels of TNF-α were measured in the sciatic nerve as an index of inflammation. Chronic constriction injury led to significant development of cold allodynia; mechanical and heat hyperalgesia; dynamic mechanical allodynia; spontaneous pain and foot deformity along with rise in the levels of TNF-α. Administration of vincristine was associated with the development of allodynia and hyperalgesia without spontaneous pain, foot deformity and elevation in the levels of TNF-α. Administration of spironolactone (10 and 20 mg/kg) significantly attenuated chronic constriction injury-induced pain related behaviour and foot deformity along with attenuation of TNF-α levels, without modulating vincristine-induced neuropathic pain. The attenuating effect of spironolactone in chronic constriction injury may be due to its anti-inflammatory properties and ability to decrease pro-inflammatory cytokines, while involvement of non-inflammatory mechanisms in the pathogenesis of vincristine-induced pain may probably explain its lack of beneficial effect in chemotherapy associated pain.

• Authors: Amteshwar Singh Jaggi, Nirmal Singh
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 648 Issue 1-3 Pg. 102-9 (Dec 01 2010) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 20846523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by Elsevier B.V.

Chemical References

• Tumor Necrosis Factor-alpha
• Spironolactone
• Vincristine

Topics

• Animals
• Constriction
• Female
• Foot Deformities (drug therapy, etiology)
• Hyperalgesia (drug therapy, etiology)
• Male
• Neuralgia (chemically induced, drug therapy, etiology, metabolism)
• Rats
• Rats, Wistar
• Spironolactone (pharmacology, therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)
• Vincristine (pharmacology)