Non-benefi cial effects of rosiglitazone in oxaliplatin-induced cold hyperalgesia in rats

Abstract

Background: Studies have suggested the ameliorative potential of PPAR  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  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  agonists are ineffective in attenuating the state of cold
hyperalgesia during oxaliplatin administration.