Pain Management and Research
Role of spinal Nrf2/HO-1 signaling pathway in hydrogen-induced reduction of inflammatory pain in rats
Wang Yuntao, Ren Lijie, Shan Shimin, Liu Xiaozhi, Chen Hongguang, Xie Keliang
Published 2018-04-20
Cite as Chin J Anesthesiol, 2018,38(4): 447-450. DOI: 10.3760/cma.j.issn.0254-1416.2018.04.017
Abstract
ObjectiveTo 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.
MethodsSixty-four SPF healthy adult male Sprague-Dawley rats, weighing 200-250 g, were divided into 4 groups (n=16 each) using a random number table: control 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 7 consecutive 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.
ResultsCompared 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).
ConclusionActivation of spinal Nrf2/HO-1 signaling pathway is involved in hydrogen-induced reduction of inflammatory pain in rats.
Key words:
NF-E2-related factor 2; Heme oxygenase-1; Spinal cord; Hydrogen; Pain; Inflammation
Contributor Information
Wang Yuntao
Department of Anesthesiology, Tianjin Fifth Central Hospital, Tianjin 300450, China
Ren Lijie
Department of Anesthesiology, Tianjin Fifth Central Hospital, Tianjin 300450, China
Shan Shimin
Department of Anesthesiology, Tianjin Fifth Central Hospital, Tianjin 300450, China
Liu Xiaozhi
Central Laboratory, Tianjin Fifth Central Hospital, Tianjin 300450, China
Chen Hongguang
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China
Xie Keliang
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China
