TY - JOUR
T1 - Nitrendipine blocks the nociceptive effects of chronically administered ethanol
AU - Gatch, Michael B.
PY - 2002/8
Y1 - 2002/8
N2 - Background: Calcium channel blockers prevent the development of tolerance to ethanol and prevent seizures and other signs of ethanol withdrawal. Calcium channels may also mediate the development of tolerance to the antinociceptive effects of ethanol. Methods: A radiant-heat tail-flick assay was used to assess the effects of nitrendipine, a dihydropyridine L-type calcium channel blocker, on ethanol-induced changes in nociception in rats. Chronic effects of ethanol were tested in four groups of rats, which received 10 days of exposure to a liquid diet. The groups received twice-daily injections of saline or nitrendipine (1, 5, or 10 mg/kg). Tail-flick latencies were measured on days 0 (baseline), 2, 4, 6, 8, and 10 and at 12 hr after removal of the liquid diet. Results: Chronic exposure to ethanol produced maximal levels of antinociception by day 4 of exposure. The observed level of antinociception gradually decreased to baseline levels by day 8. Marked decreases in tail-flick latencies below baseline (hyperalgesia) were observed during ethanol withdrawal. Repeated administration of nitrendipine blocked the antinociceptive effects of chronic ethanol and prevented the hyperalgesia produced by ethanol withdrawal. The highest dose of nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet. Conclusions: L-type calcium channel blockers block hyperalgesia during ethanol withdrawal and may mediate, at least in part, the antinociceptive effects of chronic ethanol.
AB - Background: Calcium channel blockers prevent the development of tolerance to ethanol and prevent seizures and other signs of ethanol withdrawal. Calcium channels may also mediate the development of tolerance to the antinociceptive effects of ethanol. Methods: A radiant-heat tail-flick assay was used to assess the effects of nitrendipine, a dihydropyridine L-type calcium channel blocker, on ethanol-induced changes in nociception in rats. Chronic effects of ethanol were tested in four groups of rats, which received 10 days of exposure to a liquid diet. The groups received twice-daily injections of saline or nitrendipine (1, 5, or 10 mg/kg). Tail-flick latencies were measured on days 0 (baseline), 2, 4, 6, 8, and 10 and at 12 hr after removal of the liquid diet. Results: Chronic exposure to ethanol produced maximal levels of antinociception by day 4 of exposure. The observed level of antinociception gradually decreased to baseline levels by day 8. Marked decreases in tail-flick latencies below baseline (hyperalgesia) were observed during ethanol withdrawal. Repeated administration of nitrendipine blocked the antinociceptive effects of chronic ethanol and prevented the hyperalgesia produced by ethanol withdrawal. The highest dose of nitrendipine (10 mg/kg, twice daily) reduced consumption of the ethanol diet. Conclusions: L-type calcium channel blockers block hyperalgesia during ethanol withdrawal and may mediate, at least in part, the antinociceptive effects of chronic ethanol.
KW - Calcium channel blockers
KW - Ethanol withdrawal
KW - Hyperalgesia
KW - Rat
KW - Tail-flick
UR - http://www.scopus.com/inward/record.url?scp=0036667833&partnerID=8YFLogxK
U2 - 10.1111/j.1530-0277.2002.tb02654.x
DO - 10.1111/j.1530-0277.2002.tb02654.x
M3 - Article
C2 - 12198392
AN - SCOPUS:0036667833
VL - 26
SP - 1181
EP - 1187
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
SN - 0145-6008
IS - 8
ER -