Korean J Physiol Pharmacol.  2015 Mar;19(2):125-130. 10.4196/kjpp.2015.19.2.125.

Effect of the Combination of CI-988 and Morphine on Neuropathic Pain after Spinal Cord Injury in Rats

  • 1Department of Physical Therapy, Korea University College of Health Science, Seoul 136-703, Korea. junokim@korea.ac.kr
  • 2Rehabilitation Science Program, Korea University College of Health Science, Seoul 136-703, Korea.
  • 3Department of Physiology, Korea University College of Medicine, Seoul 136-705, Korea. ywyoon@korea.ac.kr


Cholecystokinin is known to be involved in the modulation of nociception and to reduce the efficacy of morphine analgesia. This study investigated the effects of intrathecal administration of morphine and the cholecystokinin type B antagonist CI-988 on below-level neuropathic pain after spinal cord injury in rats. We also examined the interaction of morphine and CI-988 in the antinociceptive effect. Both morphine and CI-988 given individually increased the paw withdrawal threshold to mechanical stimulation in a dose-dependent manner. The combination of ineffective doses of intrathecally administered CI-988 and morphine produced significant analgesic effects and the combination of effective doses resulted in analgesic effects that were greater than the sum of the individual effects of each drug. Thus, morphine showed a synergistic interaction with CI-988 for analgesia of central neuropathic pain.


Cholecystokinin; Morphine; Neuropathic pain; Spinal cord injury; Synergistic interaction
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