Expression of C‐fos‐like protein as a marker for neuronal activity following noxious stimulation in the rat

Abstract

C-fos is a proto-oncogene that is expressed within some neurons following depolarization. The protein product, c-fos protein, can be identified by immunohistochemical techniques. Therefore, c-fos expression might be used as a marker for neuronal activity throughout the neuraxis following peripheral stimulation. This study has analyzed patterns of c-fos expression in both control and anesthetized animals and in anesthetized rats subjected to various forms of peripheral stimulation. Labeled cells were counted in the spinal cord, brainstem, hypothalamus, and thalamus. Little c-fos immunoreactivity was found in control animals. Prolonged inhalational anesthesia increased the number of labeled cells at several brainstem sites. Noxious stimulation of anesthetized rats induced c-fos within the neuraxis in patterns consistent with data obtained from electrophysiological studies and in additional locations for which few direct electrophysiological data are available, such as the ventrolateral medulla, the posterior hypothalamic nucleus, and the reuniens and paraventricular thalamic nuclei. Gentle mechanical stimulation was ineffective in inducing c-fos-like protein. The data suggest that c-fos can be used as a transynaptic marker for neuronal activity following noxious stimulation. However, c-fos is expressed only in some kinds of neurons following peripheral stimulation, and it therefore may be an incomplete marker for nociresponsive activity. In addition, at least a few neurons express c-fos protein in the absence of noxious stimulation. Experiments analyzing c-fos expression must be designed with care, as both extraneous stimuli and anesthetic depth influence the results.

GABA enhancement of maternal defense in mice: Possible neural correlates

“…We previously have found that injections in the absence of light isoflurane impairs maternal aggression (S.C. Gammie, unpublished observations), but injections with light isoflurane could also have a minor negative impact. Previous studies have demonstrated that slight stimuli like injections (Asanuma et al, 1992;Asanuma and Ogawa, 1994;Morgan et al, 1987;Nakajima et al, 1989;Ryabinin et al, 1999;Sharp et al, 1991), anesthesia (Bullitt, 1990;Dragunow et al, 1990;Morgan et al, 1987), and handling ( Asanuma et al, 1992;Asanuma and Ogawa, 1994;Ryabinin et al, 1999) can induce c-Fos mRNA or protein in the male rodent brain. The c-Fos-IR in behaviorally-naïve mice supports the idea that injection with isoflurane itself is a stressor.…”

Nuclei-and condition-specific responses to pain in the bed nucleus of the stria terminalis

“…Similarly, we saw that the sham surgical procedure altered acute noxious stimulation-induced c-Fos expression in certain regions of the antBST (increased in OV and decreased in FU). It is unclear how these modifications in c-Fos expression alter antBST activity, however, given the strong correlation between noxious stimuli-induced c-Fos expression and neuronal activation, at least in the dorsal horn of the spinal cord, the most plausible hypothesis is that the change in c-Fos expression is due to modifications in neuronal responding, habituation or sensitization in the BST (Bullitt, 1990;Coggeshall, 2005). Alternatively, noxious information from the periphery to the BST might be modified after chronic pain or sham surgery.…”

“…Alteration in signaling pathways leading to c-Fos expression could have also affected c-Fos immunoreactivity. There is, however, little evidence from the literature suggesting alterations in the signaling pathways leading to c-Fos protein expression whereas abundant evidence supports underlying modifications in neuronal activity with associated changes in behaviours (Bullitt, 1990;Coggeshall, 2005). It is unclear why the pain-induced c-Fos-IR was blunted in the FU in both CCI and shams animals, although both inflammation and simple surgical incisions alter c-Fos expression in the spinal cord (Prewitt and Herman, 1998).…”

Pentobarbital induces nocifensive hyperrflexia, not hyperalgesia in rats

“…Finally, since nocifensive reflex enhancement by pentobarbital is nitric oxide-(NO) dependent, 7 we examined the lumbar spinal cords of stimulated animals for evidence of induction of the immediate-early-gene (IEG), c-fos in the spinal cord, which is proposed to be a marker for Nmethyl-D-aspartate (NMDA) receptor-mediated, NOdependent spinal cord plasticity. [8][9][10] Here we show that despite repeated stimulation during hyperreflexia induced by pentobarbital 30 mg·kg -1 , rats showed no behavioural, reflexive, or histochemical signs of longlasting changes in nociceptive transmission.…”