The present study explores the role of
simvastatin in
vincristine-induced
neuropathic pain, which was induced by administering
vincristine (100 µg/kg i.p.) for 10 days (two 5 day cycles with 2 days pause).
Pain was assessed by determining
mechanical hyperalgesia, mechanical dynamic
allodynia, heat
hyperalgesia and cold
allodynia. Biochemically,
myeloperoxidase (MPO) activity was measured along with serum
cholesterol levels.
Simvastatin (7.5, 15 and 30 mg/kg) was administered for 14 days after administration of
vincristine.
Simvastatin (7.5 and 15 mg/kg) reversed
vincristine-induced
neuropathic pain and attenuated
vincristine-induced increase in MPO, without altering
cholesterol levels.
Simvastatin at higher dose (30 mg/kg) did not alter
neuropathic pain despite decreasing MPO levels. Furthermore, administration of
simvastatin (30 mg/kg i.p.) in
vincristine treated rats as well as it's per se administration in normal rats reduced
cholesterol levels. Per se administration of
simvastatin in normal rats produced
neuropathic pain. It is concluded that
simvastatin attenuates
neuropathic pain only at lower doses with no reduction in
cholesterol levels and anti-inflammatory effects may possibly reverse
neuropathic pain. However, despite reducing
inflammation,
simvastatin did not confer beneficial effects at higher doses at which there is reduction in
cholesterol levels, suggesting the critical role of
cholesterol in
neuropathic pain induction.