Possible modulation of PPAR-γ cascade against depression caused by neuropathic pain in rats

Sciatic nerve ligation causes neuropathic pain with chronic constriction injury (CCI). However, there is no published report on the effect of pioglitazone as an antidepressant in the treatment of depression induced by neuropathic pain with CCI in rats. The aim of this study was to evaluate the effect of pioglitazone as an antidepressant by targeting oxidative stress by the peripheral neuropathic pain model using the CCI of the sciatic nerve.

Behavioral studies were carried out to measure thermal hyperalgesia and cold allodynia as markers of neuropathic pain and force swim test for depression. These were followed by estimation of biochemical parameters which include lipid peroxidation (LPO), reduced glutathione, catalase, nitrite and superoxide dismutase (SOD) in the rat brains as a measure of oxidative stress. We administered two intraperitoneal doses of pioglitazone (4.5 and 9.0 mg/kg, i.p.) to the treated group for 28 consecutive days from the day of injury and behavioral as well as biochemical evaluations were performed.

The results suggested that the administration of pioglitazone significantly countered the neuropathic pain induced depression as interpreted through elevated pain threshold of tactile allodynia and thermal hyperalgesia followed by decreased immobility time in the 9.0 mg/kg dose group.

It may be concluded that the oxidative stress plays a critical role in the pathogenesis of neuropathic pain and depression as evidenced by the behavioral studies and the changes in the levels of lipid peroxidase, nitrite, catalase, and glutathione and SOD.