Effects of intrathecal isoflurane administration on nociception and Fos expression in the rat spinal cord

Abstract

Isoflurane has been used as an inhaled anaesthetic for nearly 30 years. Isoflurane inhalation during anaesthesia also produces an anti-nociceptive effect. Whether this occurs at the spinal or supraspinal level remains unknown. With a novel type of liquid isoflurane, the present study examined the effects of intrathecal isoflurane on the nociceptive response and Fos expression in the rat spinal cord. Thirty-six rats were randomly assigned to three groups as follows: group A (n = 6), intrathecal physiological saline 50 μl kg⁻¹; and group B and C (n = 6 each), intrathecal isoflurane at doses of 25 μl kg⁻¹ or 50 μl kg⁻¹, respectively. Noxious thermal (Hargreaves test), mechanical (von Frey test) and chemical (formalin 5%, 50 μl) stimuli were applied to a hind paw after intrathecal isoflurane injection to study its anti-nociceptive effect. In addition, the expression of Fos protein and c-fos mRNA in the spinal dorsal horns was detected by immunohistochemistry and real-time reverse transcriptase PCR, respectively. Compared with the physiological saline control, intrathecal isoflurane significantly suppressed spontaneous paw flinches in rats induced by formalin injection and paw withdrawal induced by thermal and mechanical stimuli in a dose-dependent manner. Immunohistochemistry and real-time reverse transcriptase PCR revealed that isoflurane administration inhibited formalin injection-induced c-fos expression in the spinal cord. These data suggest that isoflurane can exert anti-nociceptive effects at the spinal level by preventing neuronal activation.