Neurochemical evidence that supraspinally administered gabapentin activates the descending noradrenergic system after peripheral nerve injury.
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.
Takeuchi
Yuichi
Y
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Takasu
Keiko
K
Honda
Motoko
M
Ono
Hideki
H
Tanabe
Mitsuo
M
D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000077206:Gabapentin; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D010147:Pain Measurement; D012584:Sciatic Nerve / Q000293:injuries; D020426:Sciatic Neuropathy / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009638:Norepinephrine