Chronic pain-related behaviors in spinally injured rats: evidence for functional alterations of the endogenous cholecystokinin and opioid systems.
We have recently developed a rat model of chronic pain states after spinal cord injury. Thus, after severe, but incomplete, ischemic spinal cord injury, some rats chronically exhibited responses indicative of pain to innocuous mechanical stimuli (allodynia) in the rostral dermatomes involving the injured spinal segments. These responses have some characteristics in common with chronic central pain in patients with spinal cord injury. We now report that systemic CI988, a specific antagonist of the cholecystokinin (CCK) type B receptor, effectively relieved the allodynia-like symptom, an effect that was reversed by the opioid receptor antagonist naloxone. Furthermore, in rats which did not develop the allodynia-like symptom after spinal cord lesion, systemic naloxone induced typical allodynia. In contrast, naloxone failed to produce allodynia in normal animals. It is thus suggested that the abnormal sensory processing initiated by spinal cord ischemic lesion is under tonic opioidergic control and dysfunction of this control by the upregulated endogenous CCK system is responsible for the development of painful sensations in these rats.
Xiao-Jun
Xu
X
Departments of Laboratory Medical Science and Technology, Section of Clinical Neurophysiology, HuddingeSweden Departments of Geriatric Medicine, Karolinska Institute, HuddingeSweden Parke-Davis Neuroscience Research Centre, CambridgeUK Department of Histology and Neurobiology, Karolinska Institute, StockholmSweden.
Jing-Xia
Hao
H
Seiger
Åke
Å
Hughes
John
J
Hökfelt
Tomas
T
Wiesenfeld-Hallin
Zsuzsanna
Z
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000502:physiology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002908:Chronic Disease; D003975:Diazepam / Q000494:pharmacology; D004723:Endorphins / Q000502:physiology*; D005260:Female; D007211:Indoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008536:Meglumine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000523:psychology*; D014828:Vocalization, Animal / Q000187:drug effects
D014151:Anti-Anxiety Agents; D004723:Endorphins; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D009270:Naloxone; D008536:Meglumine; D002766:Cholecystokinin; D003975:Diazepam