Dexmedetomidine Alleviates Presurgical Anxiety-Induced Persistent Postsurgical Pain via Decreasing the Expression of Glucocorticoid Receptor

Abstract

Background: Preoperative anxiety can worsen postsurgical pain. Glucocorticoids play an important role in psychological anxiety and pain, but the effect of glucocorticoid receptor (GR) on persurgical anxiety-induced persistent postsurgical pain remains unknown.Methods: Adult male Sprague Dawley rats were randomly divided into 10 groups: control group, SPS group, incision group, 'SPS-plus-incision' group, saline group, metyrapone group, Dexmedetomidine group 1 (10 μg/kg), Dexmedetomidine group 2 (20 μg/kg), Dexmedetomidine group 3 (40 μg/kg) and Dexmedetomidine + Corticosterone group. Single-prolonged stress (SPS) was used to induce anxiety behaviors. Intraperitoneal injection of saline and dexmedetomidine was performed at 24 h after SPS and 0.5 h before incision. Intraperitoneal injection of metyrapone (25 mg/kg) was performed at 1h before SPS. Paw withdrawal mechanical threshold (PWMT) was tested at 24 h before SPS and on 1, 4, 7, 14, 21, and 28 days after incision. Corticosterone levels were determined using ELISA. The expression of GR was determined using Western blot.Results: The 'SPS-plus-incision' group decreased PWMT compared with control group and incision group from 1 to 28 days (P<0.05). SPS combined with incision increased plasma corticosterone levels compared with control group (P<0.05). A time-dependent increase in GR was also observed in 'SPS-plus-incision' group (P<0.05). Metyrapone significantly blunted the SPS-induced persistent postsurgical pain (P<0.05). Intraperitoneal administration of dexmedetomidine inhibits SPS-induced persistent pain compared with group saline (P<0.05). The expression of GR decreased after the intraperitoneal administration of dexmedetomidine (P<0.05). Pretreatment with corticosterone blocked this effect.Conclusions: Glucocorticoids contributed to presurgical anxiety-induced persistent postsurgical pain. Dexmedetomidine that decreased the expression of GR alleviated anxiety-induced persistent pain. These results indicated that dexmedetomidine may be an effective agent for preventing presurgical anxiety-induced persistent postoperative pain.  Citation: Lu Li, Zuo-Xia Zhang, Zhi-Yu Yin, Cui-E Lu, Yi-Shan Lei, Rao Sun, et al. Dexmedetomidine alleviates presurgical anxiety-induced persistent postsurgical pain via decreasing the expression of glucocorticoid receptor. J Anesth Perioper Med 2017; x: x-x. doi:10.24015/JAPM.2017.0013This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.