Modulated expression of c-Fos in the spinal cord following noxious thermal stimulation of monoarthritic rats

Abstract

Peripheral noxious stimulation evokes functional and biochemical changes in the spinal cord which results in central sensitization and hyperalgesia, but at the same time also induces the activation of inhibitory control systems. The purpose of the present study was to investigate whether the adaptive changes induced by ongoing peripheral inflammation influence the spinal cord expression of c-Fos (a commonly used marker of neuronal activity) following an additional acute noxious stimulus. Therefore, the spinal expression of c-Fos was immunohistochemically investigated following noxious thermal stimulation of a rat monoarthritic hindpaw at various time points (1, 4, 8, 21 days) after induction of monoarthritis. Compared to normal rats, c-Fos expression following ipsilateral noxious thermal stimulation of monoarthritic rats was strongly modified in the deep laminae of the dorsal horn depending on the time course of inflammation. At 1 day of monoarthritis, an enhanced ipsilateral expression (135% and 208% of normal rats in laminae III-VI and VII, respectively) and at 3 weeks a reduced expression (38% and 23% of normal rats in laminae III-VI and VII, respectively) was detected. The amount of c-Fos-positive neurons in the ipsilateral superficial laminae I and II was unchanged at all time points investigated. To assess excitability changes on the contralateral side at an early stage of inflammation, a group of monoarthritic rats received a contralateral noxious stimulus at day 1 of monoarthritis. This resulted in a potentiated expression of c-Fos ipsilateral to the acute noxious stimulus (i.e., contralateral to the monoarthritic hindpaw) restricted to lamina II (137% of normal rats) of the dorsal horn. The data showed that changes in c-Fos expression depended on the time point of noxious heat stimulation (NHS) of monoarthritic rats, and differed in the ipsi- and contralateral side of the spinal cord. In addition to a possible habituation of c-Fos expression, it may be speculated that the time course-dependent changes reflect laminae-specific modulations of excitatory and inhibitory mechanisms during monoarthritis. Further studies are necessary in order to provide more insights into the contribution of these mechanisms on noxious stimulus-evoked c-Fos expression.

Dynamic variations of c‐Fos expression in the spinal cord exposed to intramuscular hypertonic saline‐induced muscle nociception

“…Numerous studies have observed the acute pattern of spinal c‐Fos distribution and expression in response to various noxious stimuli, such as thermal (Hunt et al., ; Herdegen et al., ; Leah et al., ; Schadrack et al., ), mechanical (Leah et al., ; Sun et al., ) and chemical insults (Herdegen et al., ; Honoré et al., ; Li et al., ). In the current study, after the i.m.…”

Use of c-fos to identify activity-dependent spinal neurons after stepping in intact adult rats

“…Past research shows that noxious stimuli such as electrical stimulation and inflammation induce c-fos specifically only in laminae I-III and not in lamina IX of the ventral horn (VH). 26,27 Therefore, the rats that underwent noxious stimuli were used only to examine locomotor-associated c-fos activation in the VH. Fatigue-induced c-fos studies in the past have identified c-fos þ neurons in the dorsal horn (DH) only.…”