c-fos and CRF receptor gene transcription in the brain of acetic acid-induced somato-visceral pain in rats.
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.
Groupe d'Etude du Stress et des Interactions Neuro-Digestives (GESIND, EA3744), Hôpital Albert Michallon, Centre Hospitalier Universitaire, 38043 Grenoble Cedex 09, France Département d'Hépato-Gastroenterologie, Hôpital Albert Michallon, Centre Hospitalier Universitaire, 38043 Grenoble Cedex 09, France.
Valérie
V
Sinniger
Christophe
C
Porcher
Patrick
P
Mouchet
Aurélie
A
Juhem
Bruno
B
Bonaz
D019342:Acetic Acid / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016762:Genes, fos; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014781:Viscera / Q000187:drug effects / Q000378:metabolism; D000099052:CRF Receptor, Type 1
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D019342:Acetic Acid