Cholecystokinin (CCK) released in the CNS inhibits the
analgesic action of exogenous
opioids and may antagonize
analgesia resulting from the activation of an endogenous
pain inhibitory system. The aim of this study was to analyse the central action of
PD 140.548 N-methyl-D-glucamine--a
peptide antagonist of a specific peripheral type
CCK receptor--on animal behaviour,
catecholamines (CA) and
cortisol concentration, as well as clinical symptoms of
visceral pain induced by duodenal distension (DD). A 5 min distension of the duodenum wall, using
a 10 cm long balloon filled with 40 and/or 80 ml of water (DD 40 and/or DD 80) at animal body temperature, produced a significant increase in plasma CA and
cortisol levels, an increase in the heart rate,
hyperventilation and other clinical symptoms (inhibition of rumen motility, bleating, teeth grinding, prostration, urination, defecation) that may be related to
pain, proportionally to the degree of intestinal distension. Intracerebroventricular administration of PD 140.548 at the dose of 1 or/and 2 mg in
toto 10 min before applying DD 40 completely blocked the increase in blood plasma
cortisol,
epinephrine (E),
norepinephrine (NE) and
dopamine (DA) concentration. It is suggested that the central inhibitory action of CCK antagonist on the
cortisol and
catecholamine release produced by
visceral pain is due to the inhibition of peripheral CCK1 type receptors in the central centrifugal descending
pain facilitatory system in sheep perhaps via the hypothalamic-pituitary-adrenal axis.