The preventive effects of dexmedetomidine on endotoxin-induced exacerbated post-incisional pain in rats

Low-grade endotoxin (lipopolysaccharide; LPS) exposure may contribute to the development of exaggerated acute postoperative pain. In the present study, we investigated the possible impact of intraoperative administration of dexmedetomidine (DEX) on LPS-induced postoperative hyperalgesia in a rat incisional pain model.

The surgical and sham-surgical animals were randomly divided into saline-treated control, 5.0 mg/kg LPS-treated, 10 µg/kg DEX-treated, and 5.0 mg/kg LPS + 10 µg/kg DEX-treated groups. In the surgical animals, a 1-cm-long plantar incision was made through the skin and fascia under isoflurane anesthesia. The sham-surgical rats were only anesthetized. All treatments were administered by a single intraperitoneal (i.p.) injection 60 min before surgery. Acute postoperative pain was assessed using the Rat Grimace Scale (RGS) one day before surgery (baseline) and at 2 h post incision. In another experiment, the involvement of the α₂-adrenergic receptor was tested using atipamezole, an α₂-adrenergic receptor antagonist.

In the sham-surgical animals, the RGS did not increase at 2 h after sham surgery compared with the corresponding baseline values in all groups. In the surgical rats, however, the postoperative RGS value of the LPS group was significantly higher than the control group, indicating LPS-induced postoperative hyperalgesia. Administration of intraoperative DEX could prevent the development of such LPS-induced exacerbated post-incisional pain. In addition, the preventive effects of intraoperative DEX were inhibited by pretreatment with atipamezole.

Our findings indicate that intraoperative DEX treatment can prevent LPS-induced exacerbated post-incisional pain via the α₂-adrenergic receptor signaling pathway.