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Atorvastatin inhibits inflammatory hypernociception.

T Santodomingo-Garzón1, T M Cunha, W A Verri

  • 1Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

British Journal of Pharmacology
|July 26, 2006
PubMed
Summary
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Atorvastatin, a cholesterol-lowering drug, demonstrated significant pain relief in inflammatory models. Its analgesic effects stem from reducing inflammatory mediators and stimulating nitric oxide production.

Area of Science:

  • Pharmacology
  • Immunology
  • Pain Research

Background:

  • Atorvastatin is a 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor used for cardiovascular disease prevention.
  • Inflammation involves a cascade of mediators including bradykinin, TNF-alpha, IL-1beta, KC/CXCL, and PGE(2).

Purpose of the Study:

  • To investigate the analgesic effect of atorvastatin in inflammatory pain models.
  • To elucidate the mechanisms underlying atorvastatin's antinociceptive properties.

Main Methods:

  • Oral administration of atorvastatin in mouse models of inflammatory hypernociception.
  • Evaluation of mechanical hypernociception using an electronic pressure-meter.
  • Quantification of cytokines and prostaglandin E(2) via ELISA and RIA.

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Main Results:

  • Atorvastatin dose-dependently reduced hypernociception induced by lipopolysaccharide and antigen challenge.
  • Atorvastatin inhibited hypernociception and mediator release induced by bradykinin, cytokines, and lipopolysaccharide.
  • Antinociceptive effects were linked to nitric oxide synthase (NOS) activity, particularly constitutive NOS.

Conclusions:

  • Atorvastatin exhibits antinociceptive effects by inhibiting cytokine and prostanoid production.
  • Atorvastatin stimulates nitric oxide (NO) production via constitutive NOS.
  • Statins may represent a novel class of analgesic medications.