Spinal and hindbrain structures involved in visceroception and visceronociception as revealed by the expression of Fos, Jun and Krox-24 proteins.
We have used the evoked expression of the immediate early gene-encoded proteins (Krox-24, c-Fos, Fos B, Jun D, Jun B, c-Jun) to monitor visceral processing in both the spinal cord and hindbrain structures of rats undergoing either mechanical colorectal or chemical intraperitoneal stimulation. Experiments were conducted under controlled volatile anaesthesia to suppress affective reactions that visceral stimulations may induce. The results refer to the effects of anaesthesia alone, and of both innocuous and noxious stimulations. Non-nociceptive and nociceptive stimulation but not anaesthesia were effective in evoking c-Fos, c-Jun, Jun B and Krox-24 expressions in the spinal cord. Intraperitoneal injections labelled cells mostly at the thoracolumbar junction levels, while colorectal distension labelled cells mostly at the lumbrosacral junction levels. Labelling was widely distributed throughout the gray matter including superficial layers, deep dorsal horn, lamina X and sacral parasympathetic columns. Krox-24- and, to a lesser degree, c-Jun-labelled cells were quite numerous in the superficial layers of the dorsal horn; Jun B, and especially c-Fos, were very effective in demonstrating inputs to all parts of the spinal cord. Both anaesthesia and noxious visceral stimulation were effective in evoking c-Fos, Krox-24 and Jun B expressions in discrete hindbrain subregions. The structures which are primarily labelled under anaesthesia are the rostral ventrolateral medulla, the external medial and lateral nuclei of the parabrachial area, the medial and dorsal subnuclei of the nucleus of the solitary tract, the area postrema, the central gray including pars alpha and nucleus O, the nucleus beta of the inferior olive, the locus coeruleus, and the inferior colliculi and adjacent parts of central gray. The structures which are primarily labelled following noxious visceral stimulation are the caudal intermediate reticular nucleus as part of the caudalmost ventrolateral medulla and the superior lateral nucleus of the rostrolateral parabrachial area. Labelling in the caudal intermediate reticular nucleus was maximal for colorectal distension. Labelling in the superior lateral nucleus was specific to peritoneal inflammation. The Edinger-Westphal nucleus is a structure in which noxious-evoked labelling was superposed onto the anaesthesia-evoked labelling. Nociception-evoked overexpression in this nucleus was maximal for intraperitoneal inflammation. The present work demonstrates that the central effects induced by either anaesthesia or visceroception including pain can be effectively monitored through the induction of an array of immediate early genes.(ABSTRACT TRUNCATED AT 400 WORDS)
Lantéri-Minet
M
M
Institut National de la Santé et de la Recherche Médicale Unité 161, Paris, France.
Isnardon
P
P
de Pommery
J
J
Menétrey
D
D
D000769:Anesthesia, Inhalation; D000818:Animals; D015415:Biomarkers; D001931:Brain Mapping; D003106:Colon / Q000294:innervation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D017874:Immediate-Early Proteins; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010537:Peritoneum / Q000294:innervation; D010538:Peritonitis / Q000139:chemically induced / Q000503:physiopathology; D011312:Pressure; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000294:innervation; D012249:Rhombencephalon / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D013116:Spinal Cord / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014781:Viscera / Q000294:innervation*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors