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Neurochemical evidence that supraspinally administered gabapentin activates the descending noradrenergic system after peripheral nerve injury.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2007 Feb 05; Vol. 556 (1-3), pp. 69-74. Date of Electronic Publication: 2006 Nov 03. - Publication Year :
- 2007
-
Abstract
- We have previously demonstrated that gabapentin supraspinally activates the descending noradrenergic system to produce analgesic effects after peripheral nerve injury. To further establish the neurochemical basis for its supraspinally mediated analgesic action, concentrations of spinal noradrenaline, 4-hydroxy-3-methoxyphenylglycol (MHPG), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and dopamine were measured using high-performance liquid chromatography in a murine neuropathic pain model that was prepared by partial ligation of the sciatic nerve (the Seltzer model). Intracerebroventricularly (i.c.v.) administered gabapentin (100 and 300 microg) increased the spinal MHPG concentration and the MHPG/noradrenaline ratio and alleviated mechanical hypersensitivity, whereas the concentrations of noradrenaline, 5-HT, 5-HIAA and dopamine were unchanged. By contrast, i.c.v. gabapentin neither affected the spinal MHPG concentration and MHPG/noradrenaline ratio nor exhibited analgesic effects in animals subjected to a sham operation. In addition, spinal monoamine levels in ligated animals were not changed after intrathecal administration of gabapentin which however generated analgesic effects. Thus, the supraspinally mediated analgesic effects of gabapentin are correlated with an increase in spinal noradrenaline turnover.
- Subjects :
- Amines administration & dosage
Analgesics administration & dosage
Animals
Chromatography, High Pressure Liquid
Cyclohexanecarboxylic Acids administration & dosage
Gabapentin
Hydroxyindoleacetic Acid metabolism
Injections, Intraventricular
Injections, Spinal
Male
Methoxyhydroxyphenylglycol metabolism
Mice
Pain Measurement
Sciatic Nerve injuries
Serotonin metabolism
Spinal Cord metabolism
gamma-Aminobutyric Acid administration & dosage
Amines pharmacology
Analgesics pharmacology
Cyclohexanecarboxylic Acids pharmacology
Norepinephrine metabolism
Pain metabolism
Sciatic Neuropathy metabolism
gamma-Aminobutyric Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 556
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 17141754
- Full Text :
- https://doi.org/10.1016/j.ejphar.2006.10.059