Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain.
BACKGROUND
Gabapentin, a gamma-aminobutyric acid analog anticonvulsant, has been shown to possess antinociceptive effects in animal models and clinical trials. An endogenous binding site of [3H]gabapentin has been revealed to be the alpha(2)delta subunit of voltage-dependent Ca2+ channels. Magnesium chloride, ruthenium red, and spermine have been shown to modulate [3H]gabapentin binding to this binding site in vitro. In this study, the authors examined whether intrathecal magnesium chloride, ruthenium red, or spermine could affect the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain.


METHODS
Under isoflurane anesthesia, male Sprague-Dawley rats received an incision over the plantar surface of the right hind paw to produce punctate mechanical allodynia. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before incision, 2 h after incision, and every 30 min after intrathecal coadministration of gabapentin with normal saline or different doses of magnesium chloride, ruthenium red, or spermine for 2 h.


RESULTS
Intrathecal gabapentin (30, 100, 200 microg) dose-dependently reduced incision-induced allodynia. Hexahydrated magnesium chloride (5, 10, 20 microg) and ruthenium red (0.2, 2, 20 ng) noncompetitively inhibited the antiallodynic effect of gabapentin. Spermine at doses not inducing motor weakness (30, 60 microg) did not affect the antiallodynic effect of gabapentin. The antiallodynic effect of intrathecal morphine (1.5 microg) was not affected by hexahydrated magnesium chloride (20 microg), ruthenium red (20 ng), or spermine (60 microg).


CONCLUSIONS
These results provide behavioral evidence to support that the alpha(2)delta subunit of Ca2+ channels may be involved in the antiallodynic action of intrathecal gabapentin in the postoperative pain model.
Cheng
Jen-Kun
JK
Department of Anesthesiology, Mackay Memorial Hospital and Taipei Medical University, Taiwan.
Lai
Yu-Jun
YJ
Chen
Chien-Chuan
CC
Cheng
Ching-Rong
CR
Chiou
Lih-Chu
LC
D000085:Acetates / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000588:Amines; D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D006930:Hyperalgesia / Q000188:drug therapy* / Q000523:psychology; D007278:Injections, Spinal; D015636:Magnesium Chloride / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy* / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012430:Ruthenium Red / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D015636:Magnesium Chloride; D012430:Ruthenium Red; D013096:Spermine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine