Fedotozine, a kappa-opioid agonist, prevents spinal and supra-spinal Fos expression induced by a noxious visceral stimulus in the rat

Fedotozine, a kappa opioid agonist, reverses digestive ileus caused by acet ic acid (AA)-induced visceral pain in rats. The aims of this study were: to map, in conscious rats, central pathways activated by AA using Fos as a ma rker of neuronal activation; to characterize primary afferent fibres involv ed in this activation; and to investigate the effect of fedotozine on AA-in duced Fos expression. AA (0.6%; 10 mL kg(-1)) was injected i.p. in consciou s rats either untreated; pretreated 14 days before with capsaicin; pretreat ed 20 min previously with fedotozine; or pretreated 2 h prior to fedotozine with the kappa-antagonist nor-binaltorphimine (nor-BNI). Controls received the vehicle alone. 60 min after injection of AA, rats were processed for F os immunohistochemistry. Visceral pain was assessed by counting abdominal c ramps. AA induced Fos in the thoraco-lumbar spinal cord (laminae I, V, VII and X) and numerous brain structures such as the nucleus tractus solitarius , and paraventricular nucleus (PVN) of the hypothalamus, whereas almost no Fos labelling was observed in controls. Capsaicin pretreatment blocked AA-i nduced Fos in all structures tested. Fedotozine significantly decreased AA- induced abdominal cramps and Fos immunoreactivity in the spinal cord and PV N, this effect being reversed by nor-BNI pretreatment. AA induces Fos in the spinal cord and numerous brain nucuei, some of which are involved in the control of digestive motility in rats. This effect is m ediated through capsaicin-sensitive afferent fibres and prevented by fedoto zine most likely through a peripheral action on visceral afferents.