Ameliorative effect of papain on behavioral and bio-chemical alterations in in-silico and In-vivo models of neuropathic pain in rats

The present study investigated the ameliorative effect of Papain (PN) on N-methyl D-aspartate (NMDA) receptor down-regulation pathway by using in-silico studies and on oxidative stress in-vivo model of neuropathic pain in rats via partial sciatic nerve ligation (PSNL). In-silico molecular docking study of Papain with NMDA receptors was carried out especially with active pocket of NR2B to know its binding affinity. In in-vivo studies, briefly the rats were randomly divided into sham, vehicle, Pregabalin (standard) and PN treated groups. PSNL was carried out in vehicle and PN treated rats but not in sham and PN (100) treatment control group. PN 50 and 100 mg/kg was administered for a period of 21 days after PSNL. Behavioral alterations were assessed by foot deformity score, cold-allodynia and motor co-ordination tests. On 21st day after behavioral assessment, the rats were sacrificed; sciatic nerve was collected for biochemical estimations of superoxide dismutase (SOD), catalase (CAT), lipid peroxide levels (MDA) and glutathione reductase (GR) levels. In-silico studies revealed that affinity of ligand PN with the NR2B (NMDA) receptor showed best antagonistic effects compared to standard pregabalin. From In-vivo studies, it was observed that PN was significantly (p<0.001) attenuated PSNL induced in behavior and biochemical changes indicating its neuroprotection through antioxidant and antiglutaminergic mechanisms.