Effects of anesthetic propofol on release of amino acids from the spinal cord during visceral pain

As one of general anesthetics, propofol, has been used for surgical procedures of visceral organs. However, the mechanisms underlying the action of propofol on visceral nociception remain controversial. The aim of this study is to test whether the antinociception of systemic administration of propofol against visceral stimuli is related to the changes in release of excitatory and inhibitory amino acids in the spinal cord. The spinal microdialysis catheters were implanted subarachnoidally via the atlanto-occipital membrane in healthy SD rats. The rats received an intraperitoneal injection of acetic acid for visceral pain induction 10 min after intraperitoneal pretreatment with vehicle or propofol (100 mg/kg). The acetic acid-induced writhing assay was used to determine the degree of antinociception. Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space before pretreatment and after visceral pain induction. Visceral pain-induced release of amino acids into the dialysate, including glutamate, aspartate, and γ-amino butyric acid was evaluated by measuring the changes in the concentrations of these amino acids. Acetic acid increased release of aspartate and glutamate, and decreased release of γ-amino butyric acid in the cerebrospinal fluid as measured by microdialysis. Pretreatment with propofol significantly decreased writhing responses induced by visceral pain, suppressed the visceral pain-induced aspartate and glutamate release, and reversed the decreased release of γ-amino butyric acid in the cerebrospinal fluid. These data provide evidence for a potential mechanism for the antinociceptive effects of propofol on visceral nociception.