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PAIN MEDICINE

The Antiallodynic Action Target of Intrathecal Gabapentin: Ca²⁺ Channels, K_ATP Channels or N-Methyl-d-Aspartic Acid Receptors?

Jen-Kun Cheng, MD^*, Chien-Chuan Chen, MD^*, Jia-Rung Yang, BS^*, and Lih-Chu Chiou, PhD

*Department of Anesthesiology, Mackay Memorial Hospital; Institute and Department of Pharmacology, College of Medicine, National Taiwan University; Department of Anesthesiology, Taipei Medical University, Taipei, Taiwan

Address correspondence and reprint requests to Professor Lih-Chu Chiou, Department of Pharmacology, College of Medicine, National Taiwan University, No. 1, Jen-Ai Rd., Section 1, Taipei 100, Taiwan. Address e-mail to lcchiou{at}ha.mc.ntu.edu.tw.

Gabapentin is a novel analgesic whose mechanism of action is not known. We investigated in a postoperative pain model whether adenosine triphosphate (ATP)-sensitive K⁺ (K_ATP) channels, N-methyl-d-aspartic acid (NMDA) receptors, and Ca²⁺ channels are involved in the antiallodynic effect of intrathecal gabapentin. Mechanical allodynia was induced by a paw incision in isoflurane-anesthetized rats. Withdrawal thresholds to von Frey filament stimulation near the incision site were measured before and after incision and after intrathecal drug administration. The antiallodynic effect of gabapentin (100 µg) was not affected by intrathecal pretreatment with antagonists of K_ATP channels, NMDA receptors or gamma-aminobutyric acid (GABA)_A receptors. K_ATP channel openers and GABA_A receptor agonist, per se, had little effect on the postincision allodynic response. The Ca²⁺ channel blocker of N-type (-conotoxin GVIA, 0.1–3 µg), but not of P/Q-type (-agatoxin IVA), L-type (verapamil, diltiazem or nimodipine), or T-type (mibefradil), attenuated the incision-induced allodynia, as did gabapentin. Both the antiallodynic effects of gabapentin and -conotoxin GVIA were attenuated by Bay K 8644, an L-type Ca²⁺ channel activator. These results provide correlative evidence to support the contention that N-type Ca²⁺ channels, but not K_ATP channels or NMDA or GABA_A receptors, might be involved in the antiallodynic effect of intrathecal gabapentin.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999