Cholecystokinin antagonists a new way to improve the analgesia from old analgesics?

Cholecystokinin, originally thought to be confined only to the gastrointestinal tract, is now known to be co-localised in both the gastrointestinal tract and central nervous system. In animal models levels are increased after neural injury and with opioid administration. This peptide acts as an anti-opioid, and as levels increase, the extent of opioid derived antinociception decreases. Co-administration of a CCK antagonist along with an opioid is associated with an improved level of antinociception. Furthermore CCK antagonists may prevent antinociceptive tolerance with opioids and even reverse established tolerance. Human studies have now confirmed the pro-analgesic effect of some CCK antagonists. Human investigation of the effect of CCK antagonists on analgesic tolerance has yet to be performed. This review examines the available evidence that suggests a role for CCK antagonists in human pain management.