Document Detail


Neuronal hyperactivity at the spinal cord and periaqueductal grey during painful diabetic neuropathy: effects of gabapentin.
MedLine Citation:
PMID:  20056558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Painful diabetic neuropathy may be due to impairments in descending modulation of nociceptive transmission at the spinal cord. In the present study, streptozotocin diabetic rats (STZ rats) with neuropathic symptoms (mechanical hypersensitivity) were used to perform a time-course evaluation of neuronal activity at the spinal dorsal horn and at the periaqueductal grey matter (PAG), a major brainstem area of pain modulation. The expression of Fos protein, a marker of nociceptive activation, progressively increased at the spinal dorsal horn at 4 and 10 weeks. At the PAG, increases in Fos expression were detected until the 4th week, with a reversal to baseline values at 10 weeks in all areas except the ventrolateral PAG. Co-localisation of Fos with NeuN ascertained the neuronal nature of Fos-expressing cells at the spinal cord and PAG. Four weeks after diabetes induction, the effects of gabapentin (i.p. injection of 50mg/kg, daily during 3 days) were assessed. Gabapentin decreased Fos expression at the spinal cord and PAG and reversed mechanical hypersensitivity. The present study shows that diabetic neuropathy is accompanied by a progressive increase of the spontaneous neuronal activity at the spinal cord. Changes in descending modulation of nociceptive transmission from the PAG are likely to occur during diabetic neuropathy, probably with exacerbation of facilitatory actions. The effects of gabapentin in reversing the behavioural signs of diabetic neuropathy and neuronal hyperactivity in the spinal cord and PAG reinforce the central causes of diabetic neuropathy and point to the central targets of the drug.
Authors:
Carla Morgado; Patrícia Pereira Terra; Isaura Tavares
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-28
Journal Detail:
Title:  European journal of pain (London, England)     Volume:  14     ISSN:  1532-2149     ISO Abbreviation:  Eur J Pain     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-10-25     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  9801774     Medline TA:  Eur J Pain     Country:  England    
Other Details:
Languages:  eng     Pagination:  693-9     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.
Affiliation:
Institute of Histology and Embryology, Faculty of Medicine of Porto and IBMC, University of Porto, Portugal.
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MeSH Terms
Descriptor/Qualifier:
Amines / pharmacology,  therapeutic use*
Analgesics / pharmacology,  therapeutic use
Analysis of Variance
Animals
Cyclohexanecarboxylic Acids / pharmacology,  therapeutic use*
Diabetes Mellitus, Experimental / drug therapy,  metabolism,  physiopathology
Diabetic Neuropathies / drug therapy*,  metabolism,  physiopathology
Hyperalgesia / drug therapy*,  metabolism,  physiopathology
Male
Neurons / drug effects*,  physiology
Periaqueductal Gray / drug effects*,  metabolism,  physiopathology
Proto-Oncogene Proteins c-fos / metabolism
Rats
Rats, Wistar
Spinal Cord / drug effects*,  metabolism,  physiopathology
gamma-Aminobutyric Acid / pharmacology,  therapeutic use*
Chemical
Reg. No./Substance:
0/Amines; 0/Analgesics; 0/Cyclohexanecarboxylic Acids; 0/Proto-Oncogene Proteins c-fos; 56-12-2/gamma-Aminobutyric Acid; 6CW7F3G59X/gabapentin

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


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