Repeated Intrathecal Administration of Ropivacaine Hydrochloride Induces Apoptosis Via Up-Regulating of Fas/FasL Expression in the Rat Spinal Cord

Abstract

Background: Ropivacaine hydrochloride (RH) is a local anesthetic and frequently used for perioperative anesthesia and analgesia; but it has potential neurotoxicity, especially when intrathecally used repeatedly for a long time, although the exact mechanism is unclear.Methods: In this study, the expression of Factor associated suicide receptor (Fas) and its ligand (FasL) in the spinal cord cells was detected in rats receiving repeated intrathecal injection of RH. The paw mechanical withdraw threshold (MWT) was measured before and 3 days after intrathecal cannulation and 24 h after intrathecal administration. Rats received intrathecal injection of 0.5%, 1%, 2% RH at 0.12 ml/kg or saline of equal volume alone. Intrathecal injection was done 8 times with an interval of 1.5h in 12 h. The spinal cord was collected for pathological examination; TUNEL staining was used to assess the apoptosis in the spinal cord and the expression of Fas, FasL, caspase-3, and caspase-8 was detected by qPCR and Western blotting.Results: 1% and 2% RH groups significantly increased the MWT (P<0.05) and more vacuoles or edema was observed in the spinal cord after RH treatment. The apoptosis rates and expression of Fas, FasL, caspase-3, and caspase-8 increased in the RH groups (P<0.05).Conclusions: Repeated intrathecal administration of RH may cause damage to the spinal cord and induce apoptosis in the spinal cord via up-regulating Fas/FasL expression.