Effects of a bupivacaine nerve block on the axonal transport of Tumor Necrosis Factor-alpha (TNF-α) 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-α) occurs in case of neuropathic pain induced by nerve ligation. We used an in vivo preparation with injection of carrageenan and fluorescent TNF-α in the territory of the saphenous nerve of rats to study this transport. We have shown that retrograde transport of TNF-α 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-α. In addition, bupivacaine at low concentrations (1–10 μM) was able to stop the axonal transport ex vivo. Tetrodotoxin was less efficacious for inhibiting the TNF-α 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.