ANTINOCICEPTIVE EFFECTS OF INTRATHECAL L-TYPE CALCIUM-CHANNEL BLOCKERS ON VISCERAL AND SOMATIC STIMULI IN THE RAT

L-type calcium channels can modulate neuronal transduction in the spin al cord. However, their role in noxious information processing in anim als that are physiologically intact has not been elucidated. We evalua ted the effects of L-type calcium channel blockers diltiazem and verap amil on somatic and visceral nociception at the level of the spinal co rd. Intrathecal catheters were inserted at the L4-5 level in Sprague-D awley rats. The tail flick (TF) test and colorectal distension (CD) te st were used to assess somatic and visceral antinociceptive effects, r espectively. Motor function was assessed by posture and muscle tone in the limbs. TF latency and do threshold were measured before and for 1 80 min after the intrathecal administration of verapamil (50, 100, 300 , and 500 mu g), diltiazem (100, 300, 500, and 1000 mu g), or isotonic sodium chloride solution. The per cent maximal possible effect (%MPE) was calculated by transforming response threshold in TF and CD tests. Intrathecally administered diltiazem or verapamil increased both TF l atency and CD threshold in a dose-dependent fashion. Isotonic sodium c hloride solution, diltiazem 100 mu g, and verapamil 50 mu g did not in crease %MPE in either test. Diltiazem 300 or 500 mu g or verapamil 300 or 500 mu g significantly (P < 0.05) increased %MPE, with the peak ef fects 5 min after administration and short-duration antinociception. % MPE was 100% until 15 min after the administration of diltiazem 1000 m u g, and significant antinociception continued until 180 min in the TF test. Motor paralysis was observed after the administration of the la rger dose of each drug. We demonstrated that intrathecally administere d L-type calcium channel blockers diltiazem or verapamil produced both somatic and visceral antinociception and motor block dose-dependently . Implications: We examined the effects of intrathecally administered L-type calcium channel blockers diltiazem and verapamil on somatic and visceral nociception in rats. L-type calcium channel blockers produce d antinociceptive effects, suggesting a possible clinical application to control pain.