Cholecystokinin and enkephalin in brain stem pain modulating circuits

Neurons in rostral ventromedial medulla and the periaqueductal gray modulate dorsal horn nociceptive transmission. Endogenous peptides implicated in this modulation include enkephalin (ENK), which is antinociceptive, and cholecystokinin (CCK), which has anti-opioid effects. In this study double-label fluorescence immunocytochemistry demonstrated somata and terminals with ENK- or CCK-like immunoreactivity in these regions. Although the distribution of CCK- and ENK-immunoreactive terminal fields overlapped significantly, co-localization was rare. Furthermore, CCK- and ENK-immunoreactive somata had different morphologies and distinct distributions. The overlap of CCK- and ENK- immunoreactive terminals arbors provides a morphological substrate for an antagonistic interaction of CCK and ENK within brainstem pain modulating circuits, as has been demonstrated in the spinal cord.