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Third-party-funded project

Title:
Cytokines and hyperalgesia: studies on pathogenesis using the nerve constriction model

Project management at the University of Würzburg:

Participating scientists:

Abstract:
Proinflammatory cytokines are involved in the development of hyperalgesia and pain in inflammation and nerve lesions. We used the model of unilateral incomplete lesion of the sciatic nerve with loosely constrictive ligatures (CCI) was used in rats and mice tho show with immunohistochemistry and ELISA that endoneurial tumor necrosis factor alpha (TNF) is rapidly increased after a nerve lesion. Hyperalgesia after nerve lesion could be reduced by the early administration of inhibitors of TNF production or release. These results led to the question of the mechanisms by which TNF induces hyperalgesia after nerve lesion. Our studies, using a variety of different methods, could show that hyperalgesia after CCI is mediated by TNF receptor 1, that the adhesion molecule ICAM and the inducible cyclooxygenase COX-2 are involved, that TNF is anterogradely transported to muscle and that it induces pain there. Sural nerve biopsies of patients with painful and painless neuropathies showed a correlation of cytokine immunoreactivity and the degree of pain.

Key words:
    Neuropathic pain
    Cytokines
    knock-out mice
    Cyclooxygenase

Projekt period: from 01.1998 to 12.2000

Funding institution:
DFG ,Granting date: 01.01.1998

Preceding project:
Die Rolle von Zytokinen bei der Entstehung von Neuropathieschmerz, DFG, So 328/2-1 1996-1998

Publications: