Magnesium chloride and ruthenium red attenuate the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain.

Abstract

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.

• Authors: Jen-Kun Cheng, Yu-Jun Lai, Chien-Chuan Chen, Ching-Rong Cheng, Lih-Chu Chiou
• Journal: Anesthesiology (Anesthesiology) Vol. 98 Issue 6 Pg. 1472-9 (Jun 2003) ISSN: 0003-3022 [Print] United States
• PMID: 12766660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Amines
• Analgesics
• Analgesics, Opioid
• Calcium Channels
• Cyclohexanecarboxylic Acids
• Receptors, N-Methyl-D-Aspartate
• Magnesium Chloride
• Ruthenium Red
• Spermine
• gamma-Aminobutyric Acid
• Gabapentin
• Morphine

Topics

• Acetates (administration & dosage, antagonists & inhibitors, pharmacology)
• Amines
• Analgesics (administration & dosage, antagonists & inhibitors, pharmacology)
• Analgesics, Opioid (pharmacology)
• Animals
• Behavior, Animal (drug effects)
• Calcium Channels (drug effects)
• Cyclohexanecarboxylic Acids
• Gabapentin
• Hyperalgesia (drug therapy, psychology)
• Injections, Spinal
• Magnesium Chloride (pharmacology)
• Male
• Morphine (pharmacology)
• Pain Measurement (drug effects)
• Pain, Postoperative (drug therapy, psychology)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (drug effects)
• Ruthenium Red (pharmacology)
• Spermine (pharmacology)
• gamma-Aminobutyric Acid