Spinal glucocorticoid receptor‑regulated chronic morphine tolerance may be through extracellular signal‑regulated kinase 1/2.

Opioid use has been limited in the treatment of chronic pain due to their side effects, including analgesic tolerance. Previous studies demonstrated that glucocorticoid receptors (GRs) may be involved in the development of chronic morphine tolerance; however, the mechanism remains unknown. It was hypothesized that the expression of spinal phosphorylated mitogen‑activated protein kinase [MAPK; phosphorylated extracellular signal‑regulated kinase (ERK)] is regulated through the spinal GRs, following chronic treatment with morphine.

[Participation of glucocorticoid receptors in morphine tolerance development through the signal pathway of extracellular signal-regulated kinase].

Objective: To investigate the mechanism of glucocorticoid receptors (GR) participating in morphine tolerance development via the extracellular signal-regulated kinase (ERK) signal pathway.

Methods: Forty healthy male SD rats were implanted with intrathecal catheters and then randomized into 4 groups: Group C received an intrathecal injection of 10 µl saline, Group M 10 µg morphine, Group MR 10 µg morphine followed by 2 µg GR antagonist RU38486 and Group MD 10 µg morphine followed by 4 µg GR agonist dexamethasone (DEX) respectively. Each intrathecal drug was administered twice daily for 7 days.