Differential effect of spironolactone in chronic constriction injury and vincristine-induced neuropathic pain in rats.
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.
Jaggi
Amteshwar Singh
AS
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala-147002, India.
Singh
Nirmal
N
D000818:Animals; D003250:Constriction; D005260:Female; D005530:Foot Deformities / Q000188:drug therapy / Q000209:etiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D009437:Neuralgia / Q000139:chemically induced* / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D013148:Spironolactone; D014750:Vincristine