Pharmacological evaluation of tacrolimus (FK-506) on ischemia reperfusion induced vasculatic neuropathic pain in rats

BACKGROUND Ischemia reperfusion (I/R) is common in various pathological conditions like diabetic complication, rheumatic arthritis, necrotizing vascular occlusive disease and trauma. METHODS We have evaluated the effect of tacrolimus (1, 2 and 3 mg/kg, p.o. for 10 consecutive days) on femoral arterial ischemic reperfusion (I/R) induced neuropathic pain in rats. Behavioral parameters (i.e. hot plate, radiant heat, acetone drop, tail heat hyperalgesia, tail flick and tail cold allodynia tests) were assessed at different time intervals (i.e. 0, 1, 4, 7, 10, 13 and 16th day) and biochemical analysis in serum and tissue samples were also performed along with histopathological studies. RESULTS Behavioral pain assessment revealed increase in the paw and tail withdrawal threshold in tacrolimus treated groups against hyperalgesic and allodynic stimuli as compared to the sham control group. We observed a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels, whereas, rise in tissue reduced glutathione levels in tacrolimus treated groups. However, significant results were obtained in medium and high dose treated group as compared to sham control group. Histopathological study had revealed the increase in the neuronal edema and axonal degeneration in the I/R group whereas, tacrolimus ameliorate these effects. CONCLUSION Our results indicate the anti-oxidative, anti-inflammatory and calcium modulatory actions of tacrolimus. Therefore, it can be used as a therapeutic agent for the treatment of vascular inflammatory related neuropathic pain.