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PAIN MEDICINE

The Interaction Between Gamma-Aminobutyric Acid Agonists and Diltiazem in Visceral Antinociception in Rats

From the Department of Anesthesiology, Shimane University School of Medicine, Izumo City, Japan

Address correspondence to Kaoru Hara, MD, Department of Anesthesiology, Shimane University School of Medicine, 89–1, Enya-cho, Izumo City, 693–8501 Japan. Address email to ccy79350{at}hkg.odn.ne.jp

To examine whether the -aminobutyric acid (GABA) receptor agonists and L-type voltage-dependent calcium channel blockers potentiate each other on the visceral antinociceptive effects at the spinal cord, we assessed visceral nociception with colorectal distension (CD) test in rats with an intrathecal catheter. The measurements were performed after intrathecal administration of a GABA agonist (muscimol or baclofen), a calcium channel blocker (diltiazem), or the combination of the two. CD threshold did not change after muscimol 0.1 µg, baclofen 0.01 µg, or diltiazem 100 µg, but increased slightly after muscimol 1 µg and baclofen 0.1 µg. When muscimol 0.1 µg or 1 µg was administered with diltiazem, the increase in CD threshold was significantly larger than muscimol alone (at 5 min, 26.2% versus 0.6% MPE (maximum possible effect) or 84.5% versus 19.5%MPE, respectively; P < 0.01). The CD threshold after the combination of baclofen 0.1 µg and diltiazem also showed a significantly larger increase than that seen after baclofen alone (at 5 min, 48.0% versus 14.3% MPE; P < 0.01). Motor paralysis observed with muscimol 1 µg did not increase when muscimol was coadministered with diltiazem. In conclusion, intrathecal diltiazem in combination with a GABA agonist, muscimol or baclofen, potentiated the GABA agonists-induced visceral antinociception without increasing motor paralysis.

IMPLICATIONS: Intrathecal administration of diltiazem in combination with a -aminobutyric acid (GABA) agonist, muscimol or baclofen, potentiated the GABA agonists-induced visceral antinociception but did not affect motor paralysis. The present results indicate that the coadministration of the two types of drugs may be clinically useful.