Effects of a bupivacaine nerve block on the axonal transport of Tumor Necrosis Factor-alpha (TNF-alpha) in a rat model of carrageenan-induced inflammation.
Many pro-inflammatory cytokines are involved in the process of inflammatory pain. Bi directional axonal transport of Tumor Necrosis Factor-alpha (TNF-alpha) occurs in case of neuropathic pain induced by nerve ligation. We used an in vivo preparation with injection of carrageenan and fluorescent TNF-alpha in the territory of the saphenous nerve of rats to study this transport. We have shown that retrograde transport of TNF-alpha occurs after an inflammatory insult caused by the injection of carrageenan. This transport was likely mediated by the TNF receptor 1. A nerve block with bupivacaine totally abolishes the expression of the receptor in the dorsal root ganglion and the retrograde transport of TNF-alpha. In addition, bupivacaine at low concentrations (1-10 microM) was able to stop the axonal transport ex vivo. Tetrodotoxin was less efficacious for inhibiting the TNF-alpha transport and the rise in receptor expression and for inhibiting the axonal transport ex vivo. This may partly explain the efficacy of nerve blocks with bupivacaine to decrease the neurogenic inflammation and in a lower extent the long-term inhibition of hyperalgesic phenomenon observed in animals and in humans.
Univ. Paris-Sud, Laboratoire d'Anesthésie, UMR 788, Faculté de Médecine, F-94276 Le Kremlin Bicêtre, France.
Stéphane
S
Deruddre
Evelyne
E
Combettes
Jean-Pierre
JP
Estebe
Jacques
J
Duranteau
Dan
D
Benhamou
Hélène
H
Beloeil
Jean-Xavier
JX
Mazoit
D000779:Anesthetics, Local / Q000008:administration & dosage*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000276:immunology*; D002045:Bupivacaine / Q000494:pharmacology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004487:Edema / Q000276:immunology; D005267:Femoral Nerve / Q000187:drug effects; D005453:Fluorescence; D005528:Foot / Q000473:pathology; D005727:Ganglia, Spinal / Q000276:immunology / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D009407:Nerve Block / Q000379:methods; D020078:Neurogenic Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011134:Polysaccharides; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*
D000779:Anesthetics, Local; D011134:Polysaccharides; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D013779:Tetrodotoxin; D002351:Carrageenan; D002045:Bupivacaine