Environmental influences on viscero(noci)ceptive brain activities: the effects of sheltering

Visceral disorders are always accompanied by pain and/or a sense of ill-being that entails people to isolate themselves both physically and socially. By analogy with what happens in human beings, we have transferred to the rat the question of whether a protective, dark and quiet environment would influence the brain activities induced by visceral chemically-induced (cyclophosphamide [CP], 100 mg/kg/ip) adverse conditions of life. CP is an antitumoral drug that induces severe side effects (cystitis, headache, nausea, photophobia, phonophobia) and produces a strong state of ill-being in human beings. Brain activities were quantified using the expression of the Fos protein, a molecular marker of neuronal activity. The results compare data from groups of paired animals having been offered a shelter or not. Data were collected 4 h after the injection of CP, i. e., when cystitis was fully developed. Sheltered and unsheltered groups did not differ in bladder pathology. Intentional sheltering was shown to attenuate the expression of the CP-related Fos-Li activity within the locus coeruleus (LC) without affecting that of the structures known preferentially to process nociceptive inputs of bladder origin (dorsal vagal complex, ventrocaudal bulbar reticular formation, nucleus centralis of amygdala, dorsolateral portion of bed nucleus of stria terminalis). The LC levels of tyrosine hydroxylase and galanin neuronal contents were not affected. The LC belongs to the emotional activation system and can respond to a wide range of somatosensory and viscerosensory stimuli. Our hypothesis is that the LC would be processing the nervous activities that accompany the sense of ill-being coming from adverse conditions of life, including visceral disorders, and that voluntary isolation, by reducing its activity, would enable animals to minimize their level of distress.