Document Detail


Central inhibitory dysfunctions: mechanisms and clinical implications.
MedLine Citation:
PMID:  10097004     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Injury to the central or peripheral nervous system is often associated with persistent pain. After ischemic injury to the spinal cord, rats develop severe mechanical allodynia-like symptoms, expressed as a pain-like response to innocuous stimuli. In its short-lasting phase the allodynia can be relieved with the gamma-aminobutyric acid (GABA)-B receptor agonist baclofen, which also reverses the hyperexcitability of dorsal horn interneurons to mechanical stimuli. Furthermore, there is a reduction in GABA immunoreactivity in the dorsal horn of allodynic rats. Clinical neuropathic pain of peripheral and central origin often cannot be relieved by opiates at doses that do not cause side effects. The loss of sensitivity to opiates may be associated with the up-regulation of endogenous antiopioid substances, such as the neuropeptide cholecystokinin (CCK). CCK and its receptor (CCK-R) protein is normally not detectable in rat dorsal root ganglion cells. After peripheral nerve section, both CCK and CCK-R are up-regulated in the dorsal root ganglia. Furthermore, CI 988, an antagonist of the CCK-B receptor, chronically coadministered with morphine, reduces autotomy, a behavior that may be a sign of neuropathic pain following peripheral nerve section. Thus, opiate insensitivity may be due to the release of CCK from injured primary afferents. Similarly, in the chronic phase of the spinal ischemic model of central pain, the allodynia-like symptom is not relieved by systemic morphine, but is significantly reversed by the CCK-B antagonist. Consequently, up-regulation of CCK and CCK-R in the CNS may also underlie opiate drug insensitivity following CNS injury. Thus, dysfunction of central inhibition involving GABA and endogenous opioids may be a factor underlying the development of sensory abnormalities and/or pain following injury to neural tissue.
Authors:
Z Wiesenfeld-Hallin; H Aldskogius; G Grant; J X Hao; T Hökfelt; X J Xu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Behavioral and brain sciences     Volume:  20     ISSN:  0140-525X     ISO Abbreviation:  Behav Brain Sci     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1999-04-14     Completed Date:  1999-04-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7808666     Medline TA:  Behav Brain Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  420-5; discussion 435-513     Citation Subset:  IM    
Affiliation:
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge, Sweden. zswh@bimd01.hs.sll.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Baclofen / pharmacology,  therapeutic use
Central Nervous System / drug effects,  injuries*,  physiopathology*
Cholecystokinin / drug effects,  physiology
GABA Agonists / pharmacology,  therapeutic use
Hormone Antagonists / pharmacology
Indoles / pharmacology
Ischemia / drug therapy
Meglumine / analogs & derivatives,  pharmacology
Narcotics / pharmacology,  therapeutic use
Neural Inhibition / drug effects,  physiology*
Pain / diagnosis,  drug therapy,  etiology
Pain Measurement
Peripheral Nervous System / drug effects,  injuries,  physiopathology
Rats
Receptors, GABA / drug effects,  physiology
Spinal Cord / blood supply
Spinal Cord Injuries / complications
Chemical
Reg. No./Substance:
0/GABA Agonists; 0/Hormone Antagonists; 0/Indoles; 0/Narcotics; 0/Receptors, GABA; 1134-47-0/Baclofen; 130404-91-0/PD 134308; 6284-40-8/Meglumine; 9011-97-6/Cholecystokinin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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