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 timedependent 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.