OPEN IN READ APP
JOURNAL ARTICLE

Atorvastatin inhibits inflammatory hypernociception

T Santodomingo-Garzón, T M Cunha, W A Verri, D A R Valério, C A Parada, S Poole, S H Ferreira, F Q Cunha
British Journal of Pharmacology 2006, 149 (1): 14-22
16865092

BACKGROUND AND PURPOSE: Atorvastatin is an inhibitor of the enzyme 3-hydroxyl-3-methylglutaryl coenzyme A reductase used to prevent coronary heart disease. We have studied the analgesic effect of atorvastatin in inflammatory models in which a sequential release of mediators (bradykinin, (BK), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine, KC/CXCL) links the stimulus with release of directly acting hypernociceptive mediators such as prostaglandin E(2) (PGE(2)).

EXPERIMENTAL APPROACH: The effects of orally administered atorvastatin on inflammatory mechanical hypernociception in mouse paws were evaluated with an electronic pressure-meter. Cytokines and PGE(2) were measured by ELISA and RIA.

KEY RESULTS: Treatment with atorvastatin for 3 days dose-dependently reduced hypernociception induced by lipopolysaccharide (LPS) or that following antigen challenge in sensitized animals. Atorvastatin pre-treatment reduced hypernociception induced by bradykinin and cytokines (TNF-alpha, IL-1beta and KC), and the release of IL-1beta and PGE(2) in paw skin, induced by lipopolysaccharide. The antinociceptive effect of atorvastatin on LPS-induced hypernociception was prevented by mevalonate co-treatment without affecting serum cholesterol levels. Hypernociception induced by PGE(2) was inhibited by atorvastatin, suggesting intracellular antinociceptive mechanisms for atorvastatin. The antinociceptive effect of atorvastatin upon LPS- or PGE(2)-induced hypernociception was prevented by non-selective inhibitors of nitric oxide synthase (NOS) but not by selective inhibition of inducible NOS or in mice lacking this enzyme.

CONCLUSIONS AND IMPLICATIONS: Antinociceptive effects of atorvastatin depend on inhibition of cytokines and prostanoid production and on stimulation of NO production by constitutive NOS. Our study suggests that statins may constitute a novel class of analgesic drugs.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
16865092
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"