J Korean Med Sci.  2003 Apr;18(2):255-261. 10.3346/jkms.2003.18.2.255.

Spinal Gabapentin and Antinociception: Mechanisms of Action

• Yoon MH
• Choi JI
• Jeong SW

• KMID: 2157631
• DOI: http://doi.org/10.3346/jkms.2003.18.2.255

Abstract

Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.

Keyword

Analgesics, Non-Narcotic; Gabapentin; Injections, Spinal

MeSH Terms

Acetic Acids/administration & dosage
Acetic Acids/metabolism
Acetic Acids/pharmacology*
Adrenergic Antagonists/metabolism
Adrenergic alpha-Antagonists/metabolism
Analgesics/administration & dosage
Analgesics/metabolism
Analgesics/pharmacology*
Animals
Atropine/metabolism
Dihydroergocristine/metabolism
Enzyme Inhibitors/metabolism
Excitatory Amino Acid Agonists/metabolism
GABA Antagonists/metabolism
Injections, Spinal
Leucine/metabolism
Male
Mecamylamine/metabolism
Muscarinic Antagonists/metabolism
N-Methylaspartate/metabolism
Naloxone/metabolism
Narcotic Antagonists/metabolism
Nicotinic Antagonists/metabolism
Pain Measurement
Quinazolines/metabolism
Rats
Rats, Sprague-Dawley
Serine/metabolism
Spinal Cord/drug effects*
Thapsigargin/metabolism
Triazoles/metabolism
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism