title: Changes in pain perception during treatment with angiotensin converting enzyme-inhibitors and angiotensin II type 1 receptor blockade.
abstract: OBJECTIVE
  Besides the well-known role of the angiotensin system in blood pressure control, an interaction of angiotensin and pain perception has been suggested. This study sought to investigate whether an angiotensin converting enzyme inhibitor, which facilitates bradykinins, algesic peptides, and/or an AT1 receptor antagonist may modify hypertension-related hypoalgesia in humans. The study was approved by the ethical committee of our Department.
  
  
  METHODS
  A total of 22 hypertensive patients were submitted to dental pulp stimulation to obtain the dental pain threshold and tolerance, and to 24 h blood pressure monitoring together with a control group of 55 normotensives. Then the hypertensives were randomized to enalapril or losartan treatment and were re-evaluated (dental pain perception and ambulatory monitoring) after 8 weeks of the first treatment and after an additional 8 weeks of the second treatment.
  
  
  RESULTS
  Untreated hypertensives showed a reduced perception to painful stimuli when compared with normotensives. A significant reduction of both pain threshold and tolerance was observed during the anti-hypertensive treatments (Friedman test: P = 0.007 and P = 0.006, respectively). Pain sensitivity was similar during the two treatments and it did not differ from pain sensitivity values of normotensive controls. ANCOVAs were computed to evaluate the relationship between anti-hypertensive agents and pain sensitivity, after controlling for blood pressure. A 24 h mean pressure served as covariate, removing any effect of blood pressure; a significant difference was observed entering both pain threshold and tolerance as dependent variables (F = 5.28, P = 0.0076; F = 8.16, P = 0.0007, respectively).
  
  
  CONCLUSIONS
  Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.
authors.affiliation: Department of Clinical and Biological Sciences, University of Insubria, Varese, Italy. luigina.guasti@uninsubria.it
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.forename: Danilo
authors.initials: D
authors.lastname: Zanotta
authors.forename: Alessio
authors.initials: A
authors.lastname: Diolisi
authors.forename: Deborah
authors.initials: D
authors.lastname: Garganico
authors.forename: Cinzia
authors.initials: C
authors.lastname: Simoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudio
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grandi
authors.forename: Achille
authors.initials: A
authors.lastname: Venco
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003782:Dental Pulp / Q000503:physiopathology; D004558:Electric Stimulation; D004656:Enalapril / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects*; D044140:Receptor, Angiotensin, Type 1; D012016:Reference Values
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D004656:Enalapril; D019808:Losartan