c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats

Abstract

We aimed to characterize neuronal and corticotrophin-releasing (CRF) pathways in a model of somato-visceral pain in rats. Male rats received an intraperitoneal (i.p.) injection of either vehicle (controls) or acetic acid (AA) and were sacrificed 1, 2, 3, 4, or 6 h later. Coronal frozen sections of the brain were cut and mRNAs encoding the rat c-fos, CRF(1), CRF(2 alpha,beta) receptors were assayed by in situ hybridisation histochemistry. Localization of these transcripts within CRF-immunoreactive (i.r.) neurons of the paraventricular nucleus (PVN) of the hypothalamus was also determined. AA i.p. induced c-fos mRNA expression in brain nuclei involved in the autonomic, behavioural and neuroendocrine response to pain. Some of these nuclei are involved in the control of digestive motility, as represented by the PVN, locus coeruleus and nucleus tractus solitarius. CRF pathways, in particular in the PVN, are activated in this model. Indeed, a robust signal of c-fos and CRF(1) transcripts was observed in the PVN and numerous CRF-i.r. neurons expressed c-fos or CRF(1) transcripts in the PVN of AA-treated animals. In contrast, no expression of CRF(2) transcripts was observed in the PVN either in basal conditions or after AA i.p. These data argue for an activation of CRF pathways within the PVN in this model of somato-visceral pain. The use of CRF antagonists, particularly of the CRF(1) type, should have an interest in somato-visceral pain pathology.

Activation of the corticotropin-releasing factor receptor from the basolateral or central amygdala modulates nociception in guinea pigs

“…Previous electrophysiologycal [6], biochemical [43][44][45] and behavioral findings [18,27] have suggested that amygdaloid CRF receptors are involved in nociceptive modulation. The microinjection of a nonselective antagonist of CRF receptors in the amygdala reversed the hyperalgesia induced by opioid withdrawal as evaluated by the tail flick test in rats [27].…”

The Irritable Bowel Syndrome: How Stress Can Affect the Amygdala Activity and the Brain-Gut Axis

“…The use of C-Fos expression as a marker of neuronal activation has shown that somatovisceral Sinniger, et al 2004;2005), and visceral (Wang, et al 2009) pain as well as stress-or abdominal surgery-induced GI disturbances (Bonaz and Tache 1994a;1994b;1997;Bonaz and Rivest 1998) and colitis ) induced the activation of the amygdala. In addition, the amygdala is one of the central areas from where digestive sensations are elicited in epileptic patients (Mulak, et al 2008) during intracerebral electrical stimulations.…”

“…PVN), the bed nucleus of the stria terminalis, the lateral septum, the thalamus, the periacqueductal gray, the PB, the LC, the raphe nuclei, and the dorsal vagal complex (area postrema, nucleus tractus solitarius and DMNV) (Knapska, et al 2007). All these regions have been shown to be activated in experimental models of stress, inflammation, and pain as represented by c-fos expression and/or CRF receptor mRNA induction (Bonaz and Tache 1994a;Bonaz and Rivest 1998;Porcher, et al 2004;Sinniger, et al 2004;2005) or electrical stimulations (Mulak, et al 2008). …”

Differential Mechanisms of CRF1 and CRF2 Receptor Functions in the Amygdala in Pain-Related Synaptic Facilitation and Behavior

“…Previous biochemical (Sinniger et al, 2004;Greenwood-Van Meerveld et al, 2006;Ulrich-Lai et al, 2006) and behavioral (Lariviere and Melzack, 2000;McNally and Akil, 2002) studies point to the amygdala as an important site of CRF-mediated pain modulation, but the role of endogenously activated CRF1 and CRF2 receptors in the amygdala is not known. The present study used a multidisciplinary approach at the system and cellular levels to determine the effects of selective CRF1 and CRF2 receptor antagonists on pain-related synaptic facilitation in the amygdala, the underlying mechanisms and behavioral consequences.…”