HYPERALGESIA IN EXPERIMENTAL NEUROPATHY IS DEPENDENT ON THE TNF RECEPTOR-1

Recent evidence points to a role of cytokines like tumor necrosis fact or-alpha (TNF) in the generation of hyperalgesia not only in inflammat ory, but also in neuropathic pain. We used the model of chronic constr ictive injury (CCI) of one sciatic nerve in the mouse to investigate w hich of the two known TNF receptors is involved in the process that le ads to hyperalgesia after nerve injury. Neutralizing antibodies to TNF , to the TNF receptor 1 (TNFR1), and to the TNF receptor 2 (TNFR2) wer e administered by epineurial injection once daily to mice with CCI. Te sting of the animals' hind paws with thermal and innocuous mechanical stimuli revealed a reduction in thermal hyperalgesia and mechanical al lodynia in mice treated with neutralizing antibodies to TNF and to TNF R1. Neutralizing antibodies to TNFR2 had no effect. We conclude that T NFR1, but not TNFR2, is mediating thermal hyperalgesia and mechanical allodynia after nerve injury. (C) 1998 Academic Press.