Effects of halothane, ketamine and nitrous oxide on dynorphin mRNA expression in dorsal horn neurons after peripheral tissue injury

Abstract

Peripheral tissue injury is known to induce changes in gene expression in spinal neurons and result in a prolonged alteration of neuronal excitability. The purpose of this study was to examine the effect of halothane on the dynorphin mRNA expression in spinal dorsal horn neurons after peripheral tissue injury by formalin injection and compare the effect to that of ketamine and nitrous oxide. Male Sprague–Dawley rats were anesthetized with 1.3% halothane, ketamine, or 67% nitrous oxide. Fifteen minutes after induction of anesthesia, rats received an intraplantar injection of 150 μl 5% formalin into the unilateral hindpaw. General anesthesia was maintained for 8 h, and the expression of preprodynorphin (PPD) and preproenkephalin (PPE) mRNAs in the spinal cord (L4-5) was examined by in situ hybridization. The degree of edema of the inflamed foot was not different among the three anesthesia groups and the control (no anesthesia) group. The number of neurons expressing PPD mRNA dramatically increased in the superficial dorsal horn ipsilateral to the formalin injection in the control group compared to the contralateral side. The number of neurons labeled for PPD mRNA in the halothane group was significantly less than the control group. However, the number of PPD mRNA-expressing neurons in both the ketamine and nitrous oxide groups was significantly less than the halothane group. The expression of PPE mRNA was not influenced by these anesthetics. These data indicate that the suppressive effect of halothane anesthesia on the induction of PPD mRNA in dorsal horn neurons was smaller than those of ketamine and nitrous oxide, suggesting an important supplemental way to control the alteration of gene expression in spinal neurons for clinical settings.