Role of spinal Nrf2/HO-1 signaling pathway in hydrogen-induced reduction of inflammatory pain in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of spinal nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in hydrogen-induced reduction of inflammatory pain in rats.Methods Sixty-four SPF healthy adult male Sprague-Dawley rats,weighing 200-250 g,were divided into 4 groups (n =16 each) using a random number tablecontrol group (group C),inflammatory pain group (group IP),inflammatory pain plus hydrogen-rich saline group (group IP+H2) and inflammatory pain plus hydrogen-rich saline plus Nrf2 inhibitor all-trans retinoic acid (ATRA) group (group IP+H2+ATRA).Chronic inflammatory pain was induced by injecting complete Freund's adjuvant (CFA) 100 μl into the plantar surface of the left hind paw in IP group and IP+H2 group.The equal volume of normal saline was given instead in group C.Hydrogen-rich saline 5 ml/kg was injected intraperitoneally once a day for 7consecutive days starting from 1 day after injecting CFA in group IP+H2 and group IP+H2+ATRA,and the equal volume of normal saline was given instead in the other groups.ATRA 7 mg/kg was injected intraperitoneally once a day for 2 consecutive days starting from 2 days before injecting CFA.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model (T0) and 1,3 and 7 days after establishing the model (T1-3).Six rats were sacrificed after the last measurement of pain threshold on day 7 after establishing the model,and the L4-6 lumbar segments of the spinal cord were removed for determination of the expression of Nrf2,HO-1 and glial fibrillary acidic protein (GFAP) by Western blot.Results Compared with group C,the MWT was significantly decreased and the TWL was shortened at T1-3,and the expression of Nrf2,HO-1 and GFAP was up-regulated in IP and IP+H2 groups (P＜0.05).Compared with group IP,the MWT was significantly increased and the TWL was prolonged at T1-3,the expression of Nrf2 and HO-1 was up-regulated,and the expression of GFAP was down-regulated in group IP+H2 (P＜0.05),and no significant change was found in the parameters mentioned above in group IP+H2+ATRA (P＞0.05).Compared with group IP+H2,the MWT was significantly decreased and the TWL was shortened at T1-3,the expression of Nrf2 and HO-1 was down-regulated,and the expression of GFAP was up-regulated in group IP+H2+ATRA (P＜0.05).Conclusion Activation of spinal Nrf2/HO-1 signaling pathway is involved in hydrogen-induced reduction of infflammatory pain in rats.