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 spinal cord. However, their role in noxious information processing in animals that are physiologically intact has not been elucidated. We evaluated the effects of L-type calcium channel blockers diltiazem and verapamil on somatic and visceral nociception at the level of the spinal cord. Intrathecal catheters were inserted at the L4-5 level in Sprague-Dawley rats. The tail flick (TF) test and colorectal distension (CD) test were used to assess somatic and visceral antinociceptive effects, respectively. Motor function was assessed by posture and muscle tone in the limbs. TF latency and CD threshold were measured before and for 180 min after the intrathecal administration of verapamil (50, 100, 300, and 500 microg), diltiazem (100, 300, 500, and 1000 microg), or isotonic sodium chloride solution. The percent maximal possible effect (%MPE) was calculated by transforming response threshold in TF and CD tests. Intrathecally administered diltiazem or verapamil increased both TF latency and CD threshold in a dose-dependent fashion. Isotonic sodium chloride solution, diltiazem 100 microg, and verapamil 50 microg did not increase %MPE in either test. Diltiazem 300 or 500 microg or verapamil 300 or 500 microg significantly (P < 0.05) increased %MPE, with the peak effects 5 min after administration and short-duration antinociception. %MPE was 100% until 15 min after the administration of diltiazem 1000 microg, and significant antinociception continued until 180 min in the TF test. Motor paralysis was observed after the administration of the larger dose of each drug. We demonstrated that intrathecally administered L-type calcium channel blockers diltiazem or verapamil produced both somatic and visceral antinociception and motor block dose-dependently.


CONCLUSIONS
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 produced antinociceptive effects, suggesting a possible clinical application to control pain.
Hara
K
K
Department of Anesthesiology, Shimane Medical University, Izumo, Japan.
Saito
Y
Y
Kirihara
Y
Y
Sakura
S
S
Kosaka
Y
Y
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013623:Tail / Q000294:innervation; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*; D014781:Viscera / Q000294:innervation
D000700:Analgesics; D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem