Combined epineurial therapy with neutralizing antibodies to tumor necrosisfactor-alpha and interleukin-1 receptor has an additive effect in reducingneuropathic pain in mice

Monotherapy with antibodies to tumor necrosis factor-alpha (TNF) or interle ukin-1 receptor 1 (IL-1R1) reduces hyperalgesia in an animal model of painf ul neuropathy. Here we investigated whether combined therapy with epineuria l anti-TNF and anti-IL-1R1 antibodies produces a further advantage. C57BL/6 mice with a chronic constrictive injury of one sciatic nerve were treated epineurially with neutralizing antibodies to either IL-1R1 or TNF alone or with a combined application of neutralizing antibodies to TNF and IL-1R1. C ombined treatment with anti-IL-1R1 and anti-TNF antibodies markedly reduced thermal hyperalgesia and mechanical allodynia more effectively than monoth erapy with either antibody. There were no detectable differences in IL-1 be ta and TNF endoneurial protein expression between animals with monotherapy and combined treatment. We conclude that combined anti-cytokine therapy may be a useful strategy in the treatment of neuropathic pain. (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.