Evidence of a key-role for histamine from mast cells in the analgesic effect of clomipramine in rats.
OBJECTIVE
We investigated the role of neuronal and mast cell histamine in the analgesic effect of clomipramine.


METHODS
Male Sprague-Dawley rats (4-6 weeks old) were used (n = 228).


METHODS
Clomipramine (10, 20 or 40 mg/kg i.p.) was injected in rats pretreated with [a] saline i.cv. or i.p., [b] alpha-fluoromethylhistidine (alpha-FMH, 200 microg i.cv.), [c] compound 48/80 (C48/80, 1 mg/kg i.p.). Other rats were pretreated with clomipramine, before C48/80.


METHODS
Antinociceptive responses were determined before and 30, 60, 90, 120 min after drug injection by tail-flick (TFT) and hot-plate (HPT) tests. Results for each treatment group are given as mean %MPE +/- SEM (Student's t-test, ANOVA).


RESULTS
Clomipramine produced no significant changes in TFT and HPT in saline- or alpha-FMH-pretreated rats. Following C48/80, clomipramine (10 and 20 mg/kg) produced a dose-related significant increase in latencies, between 30 and 120 min: 28.5 +/- 5.7 vs 8 +/- 1.6 (p < 0.05), 56 +/- 5 vs 9.2 +/- 1.9 (p < 0.01) in TFT; 31 +/- 4.3 vs 12 +/- 2.5 (p < 0.05), 46.2 +/- 6 vs 11.5 +/- 1.9 (p < 0.01) in HPT. Clomipramine (40 mg/kg, after C48/80) produced marked and persistent increase in latencies 83.2 +/- 4.2 vs 10.5 +/- 3 (p < 0.01) in TFT and 91.2 +/- 4.6 vs 10.5 +/- 3 (p < 0.01) in HPT, followed by symptoms of toxicity and death of some animals. In rats pretreated with clomipramine, C48/80 was unable to show antinociceptive effects on TFT and HPT.


CONCLUSIONS
Results suggest that the antinociceptive effect of clomipramine may depend on mast cell histamine levels.
Arrigo-Reina
R
R
Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Catania, Italy.
Chiechio
S
S
D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002997:Clomipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000494:pharmacology
D000700:Analgesics; D002997:Clomipramine; D004791:Enzyme Inhibitors; D008762:Methylhistidines; D017367:Selective Serotonin Reuptake Inhibitors; D003189:p-Methoxy-N-methylphenethylamine; C028309:alpha-fluoromethylhistidine