Increased level of cholecystokinin in cerebrospinal fluid is associated with chronic pain-like behavior in spinally injured rats

Cholecystokinin (CCK) is a physiological antagonist of opioid-mediated anti nociception and may be involved in some chronic pain states where opioids h ave reduced effect. We have previously shown in a rat model of central neur opathic pain after spinal cord injury that blockade of CCK-B receptors lead to marked pain relief. In the present study, we showed that spinally injur ed rats exhibiting chronic pain-like behaviors (aversive reaction to innocu ous mechanical and cold stimulation) had significantly elevated level of CC K like immunoreactivity in cerebrospinal fluid compared to normal rats or s pinally injured rats which did not exhibit pain-like behaviors. The increas ed level of circulating CCK in the cerebrospinal fluid may thus contribute to the maintenance of chronic pain in these rats by reducing the endogenous inhibitory tone provided by opioid peptides and may be involved in the phe nomenon of opioid insensitivity. (C) 2001 Elsevier Science Inc. All rights reserved.