Abstract
Chronic constriction injury mimics trauma induced neuropathy mainly mediated by neuroinflammation, oxidative stress and mitochondrial dysfunction. Poly ADP-ribose polymerase (PARP) inhibition has been associated with these pathways and results in various deficits in peripheral neuropathy. In the present study we investigated the effect of known PARP inhibitors 3-Aminobenzamide (3-AB) and 1,5-isoquinelinediol (ISO) against behavioral and biochemical alteration in chronic constriction injury (CCI) induced neuropathy in rats. 3-AB (At doses 10mg/kg and 30mg/kg i.p) and ISO (At doses 1mg/kg and 3mg/kg i.p) were tested in rats subjected to standard models of hyperalgesia and allodynia. Functional parameters were estimated by performing spontaneous pain assessment, foot deformity index and sciatic functional index (SFI). Treatment improved pain behavior, sciatic function and foot posture. Elevations in the levels of oxidative-nitrosative stress markers were examined in both sciatic nerve and spinal cord. It significantly reduced the levels of elevated Malondialdehyde (MDA) and nitrite in both tissues. Cleaved PARP, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclooxygenase-2 (COX-2) were elevated in the animals with CCI and were attenuated by treatment. Further molecular studies are warranted to confirm the role of PARP inhibition in experimental neuropathic and the protective effects of PARP inhibitors in nerve injury mediated pain. Chronic constriction injury mimics trauma induced neuropathy mainly mediated by neuroinflammation, oxidative stress and mitochondrial dysfunction. Poly ADP-ribose polymerase (PARP) inhibition has been associated with these pathways and results in various deficits in peripheral neuropathy. In the present study we investigated the effect of known PARP inhibitors 3-Aminobenzamide (3-AB) and 1,5-isoquinelinediol (ISO) against behavioral and biochemical alteration in chronic constriction injury (CCI) induced neuropathy in rats. 3-AB (At doses 10mg/kg and 30mg/kg i.p) and ISO (At doses 1mg/kg and 3mg/kg i.p) were tested in rats subjected to standard models of hyperalgesia and allodynia. Functional parameters were estimated by performing spontaneous pain assessment, foot deformity index and sciatic functional index (SFI). Treatment improved pain behavior, sciatic function and foot posture. Elevations in the levels of oxidative-nitrosative stress markers were examined in both sciatic nerve and spinal cord. It significantly reduced the levels of elevated Malondialdehyde (MDA) and nitrite in both tissues. Cleaved PARP, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), cyclooxygenase-2 (COX-2) were elevated in the animals with CCI and were attenuated by treatment. Further molecular studies are warranted to confirm the role of PARP inhibition in experimental neuropathic and the protective effects of PARP inhibitors in nerve injury mediated pain.
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