title: Nitrous oxide decreases substance P receptor binding in the rat spinal cord.
abstract: Synaptic transmission of substance P (SP) in the spinal cord during nitrous oxide (N2O) exposure was examined in rats. In the analgesia study, 75% N2O significantly increased tail-flick latency by 57% during the first 2-h N2O exposure and by 19% after a second 2-h N2O exposure, suggesting development of acute tolerance. In the SP content study, SP in the dorsal part of the spinal cord significantly increased by 120% at the end of first N2O exposure, but returned to the control level by the end of second N2O exposure. In the receptor binding study, N2O significantly decreased the [I]Bolton-Hunter-SP ([I]BH-SP) binding (SP-P) in laminae I-II of the dorsal horn by 19, 18, and 18% at the end of first N2O exposure, at the end of the second N2O exposure, and at 4 h after the second N2O exposure, respectively, as compared to the control. This decrease in the [I]BH-SP binding became statistically insignificant by 12 h after the second N2O exposure. In contrast, [I]Bolton-Hunter-eledoisin binding (SP-E) remained unchanged. In the equilibrium binding study, the number of SP-P receptor (Bmax) in laminae I-II of the dorsal horn significantly decreased by 24, 38, and 30% at the end of the first and at the end of the second N2O exposure, and at 4 h after the second N2O exposure, respectively, without significant changes in the affinity (Ka). The present study demonstrated that tolerance to N2O analgesia occurred during the two repeated N2O exposures. SP receptor binding decreased and remained decreased 4 h after discontinuation of N2O. This evidence is the first demonstration of the functional changes caused by N2O in SP synaptic transmission of the spinal cord.
authors.affiliation: Brain Research Unit in Anesthesiology-Resuscitology, Yamaguchi University, and Department of Anesthesiology-Resuscitology, Yamaguchi University, School of Medicine, Yamaguchi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa