title: Evidence of a key-role for histamine from mast cells in the analgesic effect of clomipramine in rats.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Catania, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Arrigo-Reina
authors.forename: S
authors.initials: S
authors.lastname: Chiechio
mesh_terms: 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
chemical_list: D000700:Analgesics; D002997:Clomipramine; D004791:Enzyme Inhibitors; D008762:Methylhistidines; D017367:Selective Serotonin Reuptake Inhibitors; D003189:p-Methoxy-N-methylphenethylamine; C028309:alpha-fluoromethylhistidine