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

Abstract

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.