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BJA Advance Access published online on September 17, 2004
British Journal of Anaesthesia, doi:10.1093/bja/aeh264
© 2004 by The Board of Management and Trustees of the British Journal of Anaesthesia
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Accepted June 8, 2004

Laboratory Investigation

Contralateral effect of amitriptyline and bupivacaine for sciatic nerve block in an animal model of inflammation

J.-P. Estebe 1*, M. E. Gentili 2, P. Le Corre 3, C. Leduc 4, J.-P. Moulinoux 4, and C. Ecoffey 5

1 Service d'Anesthésie Réanimation Chirurgicale 2, University of Rennes 1, Rennes, France; Laboratoire Optimisation Biopharmaceutique par modulation des passages transmembranaire, University of Rennes 1, Rennes, France; Laboratoire GRETAC, University of Rennes 1, Rennes, France
2 Service d'Anesthésie Réanimation Chirurgicale 2, University of Rennes 1, Rennes, France; Laboratoire GRETAC, University of Rennes 1, Rennes, France
3 Laboratoire Optimisation Biopharmaceutique par modulation des passages transmembranaire, University of Rennes 1, Rennes, France
4 Laboratoire GRETAC, University of Rennes 1, Rennes, France
5 Service d'Anesthésie Réanimation Chirurgicale 2, University of Rennes 1, Rennes, France; Laboratoire Optimisation Biopharmaceutique par modulation des passages transmembranaire, University of Rennes 1, Rennes, France

* To whom correspondence should be addressed. E-mail: jean-pierre.estebe{at}chu-rennes.fr.


  Abstract

Background. Using a carrageenan inflammation rat model, we evaluated two experimental approaches to prolong sciatic nerve block on contralateral hyperalgesia.

Method. We performed ipsilateral sciatic nerve block on the inflamed hind paw with bupivacaine-loaded microspheres suspended in dexamethasone (bupivacaine 12.5 mg) and with amitriptyline (6.25 and 12.5 mg) as ultralong-acting local anaesthetics. Bupivacaine (1.25 mg) was used as long-acting local anaesthetic and saline was used as a control. The sixth group received amitriptyline 6.25 mg intraperitoneally (n=10 for each group).

Results. The duration of ipsilateral nerve block was 2 h for bupivacaine, 7 h for amitriptyline 6.25 mg, 11 h for amitriptyline 12.5 mg and 21 h for bupivacaine-loaded microspheres in suspension with dexamethasone. Whereas contralateral hyperalgesia was not observed during block produced by bupivacaine-loaded microspheres, contralateral hyperalgesia was observed with sciatic nerve block using amitriptyline.

Conclusions. Because of the differential effect observed on the contralateral side, the mechanism underlying the prolongation of ipsilateral block with amitriptyline may not result only from a prolonged Na+ channel blockade but might be explained by a local toxic effect or lack of systemic actions.

Keywords: anaesthetics local, bupivacaine; anaesthetics local, bupivacaine-loaded microspheres; analgesics, non-opioid; model, rat; pain, mechanism.
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