Choline and Parecoxib Sodium Induced Pain Inhibition in Rats After Chronic Constriction Injury of the Sciatic Nerve

Purpose: We aimed to examine the pain inhibitory effects of systemic administration of choline and parezoxib sodium in a rat model of neuropathic pain induced by a chronic constriction injury (CCI) of the sciatic nerve, and to determine the changes of high mobility protein-1 (HMGB1) and NF-κBp65 expression in the dorsal root ganglion (DRG) after drug treatment. Methods Adult rats were randomly divided into 5 groups (N = 8/group). Sham surgery group received an intraperitoneal (i.p.) injection of saline. CCI rats received saline, choline (cho, 6, 12 and 24 mg/kg), parecoxib sodium (pare, 3, 6, 12mg/kg), or a combination of choline and parecoxib sodium with each drug delivered at a sub-effective dose. Mechanical and heat pain thresholds were measured at 30 min after drug treatment at day 3, 5, 7, 10, and 14 after CCI. In a separate study, rats were also divided into 5 groups (N = 6/group) including sham, CCI + saline, CCI + cho-6 mg/kg, CCI + pare-3mg/kg, and CCI + cho-6mg/kg + pare-3mg/kg group. After repeated drug treatment for 7 days, five rats were randomly selected in each group, and the lumbar DRGs (L4-6) were harvested for Western blot study. Results Choline significantly attenuated the mechanical and heat hypersensitivities in CCI rats at 12 and 24 mg/kg doses (P < 0.05), but was not effective at 6 mg/kg dose. Parecoxib sodium exerted significant pain inhibitory effects at 6 and 12 mg/kg doses (P < 0.05), but not at 3 mg/kg dose. Combining a low dose of choline (6 mg/kg) and parecoxib sodium (3 mg/kg) produced significant pain inhibition in CCI rats, and also reduced the expression of HMGB1 and NF-κBp65 in L4-6 DRGs. Conclusion A combination of choline and parecoxib sodium may effectively relieve neuropathic pain, and the underlying mechanisms may involve an inhibition of HMGB1/TLR4/NF-κB signaling pathway in DRG neurons.