Objective To investigate the role of 2B subunits-containing N-methyl-D-aspartate receptors (NR2B) in the arcuate nucleus in the development of inflammatory pain (IP) in rats.Methods One hundred and eight male Sprague-Dawley rats, aged 9 weeks, weighing 200-250 g, were randomly divided into 4 groups using a random number table: sham operation group (group S, n =47);group IP (n =47);dimethyl sulfoxide control group (group DMSO, n =7);selective NR2B antagonist Ro25-6981 group (group Ro25-6981, n=7).IP was induced by injecting complete Freund's adjuvant (CFA) 0.1 ml into the plantar surface of the left hindpaw.Ro25-6981 400 pmol was injected into the arcuate nucleus at 3 days after CFA injection.Seven rats in each group were selected for measurement of the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) at 1 day before CFA injection (T1) and at 2 days after CFA injection (T2), at 30 min before administration on 3rd day (T3) , at 30 min after administration on 3rd day (T4) , and on 5th day (T5).In S and IP groups, The rats were sacrificed at T1-3 and T5 , and the arcuate nucleus of the hypothalamus was removed for determination of NR2B mRNA expression (by real-time reverse transcriptase polymerase chain reaction) and NR2B and phosphorylated NR2B (p-NR2B) expression (by Western blot).Conclusion Compared with group S, the MWT was significantly decreased, and the TWL was shortened at T2-5 in IP, DMSO and Ro25-6981 groups, and the expression of p-NR2B was up-regulated at each time point (P＜0.05) , and no significant change was found in NR2B protein and mRNA expression in group IP (P＞0.05).Compared with group IP, the MWT was significantly increased, and the TWL was prolonged at T4in group Ro25-6981 (P＜0.05) , and no significant change was found in MWT and TWL at each time point in group DMSO (P＞0.05).Conclusion The activation of NR2B in the arcuate nucleus is involved in the development of IP in rats.