Spinal gabapentin and antinociception: mechanisms of action.
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.
Yoon
Myung Ha
MH
Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Korea. mhyoon@chonnam.ac.kr
Choi
Jeong Il
JI
Jeong
Seong Wook
SW
D000085:Acetates / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000588:Amines; D000700:Analgesics / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids; D025442:Dihydroergocristine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D018756:GABA Antagonists / Q000378:metabolism; D000077206:Gabapentin; D007278:Injections, Spinal; D007930:Leucine / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000378:metabolism; D016202:N-Methylaspartate / Q000378:metabolism; D009270:Naloxone / Q000378:metabolism; D009292:Narcotic Antagonists / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000378:metabolism; D010147:Pain Measurement; D011799:Quinazolines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects*; D019284:Thapsigargin / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D018733:Nicotinic Antagonists; D011799:Quinazolines; D014230:Triazoles; D025442:Dihydroergocristine; D009270:Naloxone; D012694:Serine; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D019284:Thapsigargin; D000077206:Gabapentin; D008464:Mecamylamine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D001285:Atropine; D007930:Leucine; C052410:9-chloro-2-(2-furyl)-(1,2,4)triazolo(1,5-c)quinazolin-5-imine