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Original Article

pnr. 2011; 2(1): 28-34


Non-beneficial effects of rosiglitazone in oxaliplatin-induced cold hyperalgesia in rats

Vivek Jain, Amteshwar Singh Jaggi, Nirmal Singh.

Abstract
Background: Studies have suggested the ameliorative potential of PPAR g agonist in attenuating the nerve injury-induced neuropathic pain. However, their role in chemotherapy-induced neuropathic pain is not explored yet. Aims: To investigate the potential of rosiglitazone, a PPAR g agonist, in oxaliplatin-induced cold hyperalgesia in rats. Settings and Design: All animals were divided in nine groups and single administration of oxaliplatin (6 mg/kg ip) used for induction of neuropathy. Material and Methods : The pinprick, cold immersion, hot plate and hot immersion tests were performed to assess the degree of mechanical hyperalgesia, cold hyperalgesia, heat hyperalgesia, and heat allodynia, respectively. The levels of thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) were measured as an index of oxidative stress. The myeloperoxidase (MPO) activity (a specific marker of inflammation) and calcium levels were also determined. Statistical analysis: Two-way analysis of variance (ANOVA) followed by Bonferroni's post test for behavioral assessment and one-way ANOVA followed by Tukey's multiple range tests for biochemical assessment were performed. Results: Single administration of oxaliplatin resulted in significant development of cold hyperalgesia without altering the nociceptive threshold for mechanical and heat stimuli. Furthermore, oxaliplatin increased the oxidative stress and decreased calcium levels without affecting inflammation. Treatment with rosiglitazone (2.5, 5, and 10 mg/kg po) for 11 days did not modulate oxaliplatin-induced cold hyperalgesia. Moreover, rosiglitazone did not modulate oxaliplatin-induced biochemical changes. Conclusions: PPAR g agonists are ineffective in attenuating the state of cold hyperalgesia during oxaliplatin administration.

Key words: Cold hyperalgesia, oxaliplatin, PPAR γ, rosiglitazone



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