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PAIN MEDICINE

The Effect of Local Anesthetics and Amitriptyline on Peroxidation In Vivo in an Inflammatory Rat Model: Preliminary Reports

Christine Leduc, MSc^*, Marc E. Gentili, MD MSc, Jean-Pierre Estèbe, MD PhD, Pascal Le Corre, PharmD PhD, Jacques-Philippe Moulinoux, MD PhD^*, and Claude Ecoffey, MD

*GRETAC, Laboratoire de Biologie Cellulaire, and Laboratoire de Pharmacologie Galénique et de Biopharmacie, Université Rennes I; Département d’anesthésie-réanimation II, Clinique de la douleur, Hôpital Universitaire Hôtel-Dieu; and Département d’anesthésie-réanimation II, Hôpital Universitaire Pontchaillou, Rennes, France

Address correspondence and reprint requests to Marc Gentili, MD, MSc, Département d’anesthésie-réanimation II, Clinique de la douleur, Hôpital Universitaire Hôtel-Dieu, 35 000 Rennes, France. Address e-mail to marc.gentili{at}wanadoo.fr

We studied the inhibition of peroxidation by local anesthetics in an inflammatory animal model. Inflammatory lipid peroxidation was assessed by the thiobarbituric assay in plasma from rats injected or not injected with carrageenan (Carra) and killed 1, 2, 4, 6, 12, and 24 h thereafter. Thiobarbituric acid reactive substances (TBARS) values in inflammatory animals were maximal 6 h after Carra administration. This result, in accordance with the evolution of paw edema width during time, supports that TBARS reflect the intensity of inflammation. Local anesthetics (bupivacaine, lidocaine, ropivacaine, or bupivacaine-loaded microspheres) or amitriptyline were injected in clinically relevant concentrations as a sciatic nerve block or intraperitoneally in inflamed animals. Ropivacaine did not exhibit any protective effect on Carra-induced lipid peroxidation in rats. With all the other drugs administered as a sciatic nerve block, the maximal TBARS increase was not observed at 6 h. Our conclusion is that bupivacaine (plain or encapsulated), lidocaine, and amitriptyline in clinically relevant concentrations administered via the sciatic nerve showed antioxidant properties toward lipid peroxidation induced by Carra inflammation. Intraperitoneal injection of those drugs gave the same effect as nerve block; this result suggests that their mechanism of action is not strictly limited to the nerve.

IMPLICATIONS. We investigated the antioxidant effects of local anesthetics and amitriptyline in an inflammatory rat model. Amitriptyline exhibits antioxidant properties per se, whereas lidocaine and bupivacaine (plain or encapsulated) seem to inhibit the peroxidation process. This may have future application in limiting toxic oxygen metabolite production during the inflammatory process.

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