Abstract
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.
