Alterations of c-Fos mRNA expression in hypothalamic-pituitary-adrenal axis and various brain regions induced by intrathecal single and repeated substance P administrations in mice.

The effect of substance P (Sub P) injected intrathecally (i.t.) on c-fos mRNA expression in various tissues was examined in the present study. We found that a single administration of Sub P (0.5 nM) caused an increase of the c-fos mRNA level in the hypothalamic-pituitary-adrenal (HPA) axis, hippocampus, and spinal cord. The time-course study showed that c-fos mRNA level was maximal at 10 min and began to decrease 30 min after the Sub P injection in all tissues, and the Sub P-induced increase of the c-fos mRNA level was returned to the control level 1 h after the injection. The kinetics of the c-fos mRNA expression in mice that were repeatedly injected with Sub P (every 30 min interval up to 4 times) were different in the HPA axis, hippocampus, and spinal cord. The increased c-fos mRNA level in the hypothalamus and the spinal cord induced by i.t. injected Sub P remained at a high level. In the pituitary gland, adrenal gland, and hippocampus, the increased level of c-fos mRNA expression gradually returned to the control level during the repeated substance P injections up to 4 times. Our results suggest that spinally injected Sub P-induced pain stress increases c-fos mRNA expression in the spinal cord, hippocampus, and HPA axis. In mice repeatedly injected with Sub P, the kinetics of c-fos mRNA appear to be different varied from tissue to tissue.