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P3‐323: Ppar‐gamma agonist modulates the neuropathic pain and related cognitive deficits: Possible biochemical, mitochondrial evidences
Author(s) -
Pottabathini Raghavender,
Kumar Anil
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.1697
Subject(s) - neuropathic pain , morris water navigation task , allodynia , neuroinflammation , hyperalgesia , oxidative stress , medicine , palmitoylethanolamide , lipid peroxidation , neurochemical , anesthesia , elevated plus maze , malondialdehyde , pharmacology , nociception , endocrinology , agonist , hippocampus , inflammation , receptor , anxiety , cannabinoid receptor , psychiatry
Background: Chronic pain is known to be associated with the various central nervous system disorders including memory deficits and depression. Neuroinflammation and oxidative stress in coordination with mitochondrial dysfunction has been suggested to play key role in the development and maintenance of the neuropathic pain and related cognitive dysfunction. The present study was designed to explore the role of neuroinflammation, oxidative stress in the spinal nerve ligation (SNL) induced neuropathic pain and related cognitive deficit with the help of various behavioral, biochemical, mitochondrial and cellular alterations in rats. Methods: In the present study, unilateral lumbar L5 and L6 spinal nerves were ligated to induce neuropathic pain and cognitive deficits in rats. Behavioral parameters were assessed on the day before ligation and successively on day 7, 14, 21 and 28 post nerve injury. Neuroinflammatory, oxidative stress parameters and mitochondrial enzyme functions were assessed on day 28 after behavioral observations. Results: SNL resulted in significant increase in mechanical allodynia, mechanical hyperalgesia, cold allodynia and increased transfer latency as assessed by Vonfrey, Randall Selitto, Acetone drop and Elevated plus maze, Morris water maze tests respectively. SNL also resulted in significant increase in oxidative stress parameters (increased lipid peroxidation, nitrite, reduced superoxide dismutase, catalase and glutathione) in lumbar spinal cord and brain. There is also increase in inflammatory cytokines and inhibition of mitochondrial enzyme complexes activities by SNL. Pioglitazone (a PPAR gamma agonist) treatment for 28 days significantly reversed the various behavioral, biochemical and mitochondrial alterations in SNL treated animals. Conclusions: Results of the present study shown that ameliorative potential of pioglitazone in SNL induced behavioral and mitochondrial alterations which may be further attributed to inhibition of oxidative stress and mitochondrial dysfunction in rats.