Peripheral axotomy influences the in vivo release of cholecystokinin in the spinal cord dorsal horn-possible involvement of cholecystokinin-B receptors

Abstract

An increased expression of cholecystokinin (CCK) messenger RNA (mRNA) as well as CCK-B receptor mRNA in dorsal root ganglion (DRG) cells following peripheral axotomy has previously been demonstrated. In the present in vivo microdialysis study, the effect of unilateral sciatic nerve section on basal and potassium-induced release of CCK-like (CCK-LI) immunoreactivity in the rat dorsal horn was investigated. We also compared the effects of the CCK-B receptor antagonist CI988 on basal and potassium-stimulated CCK-LI release in intact animals and in chronically axotomized rats. Perfusion of the microdialysis probe with KCl (100 mM) induced a more than 6-fold increase of the extracellular level of CCK-LI in control animals. In contrast, following unilateral sciatic nerve section the same KCl stimulation failed to evoke a release of CCK-LI ipsilaterally. However, after systemic administration of CI988 (1 mg kg-1, i.v.), 100 mM KCl induced a significant increase of the extracellular CCK-LI level in axotomized rats, similar to that observed in control animals. In control animals no effect of CI988 on KCl-stimulated CCK-LI release could be detected. CI988 by itself had no influence on the extracellular CCK-LI level in either nerve injured or control animals. The present data suggest that axotomy reduces the release of CCK-like immunoreactivity in the spinal cord by a mechanism involving the CCK-B receptor binding site.