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:
- Schäfers M, Schmidt C, Vogel C, Toyka KV, Sommer C.
(2002). Tumor necrosis factor-alpha (TNF) regulates the expression of ICAM-1 predominantly through TNF receptor 1 after chronic constriction injury of mouse sciatic nerve. 2,2. (monograph)
- Sommer C, Petrausch S, Lindenlaub T, Toyka KV.
(1999). Neutralizing antibodies to interleukin 1-receptor reduce pain asociated behavior in mice with experimental neuropathy. Neurosci Lett, 2,0. (scientific article)
- George A, Schmidt C, Weishaupt A, Toyka KV, Sommer C.
(1999). Serial determination of tumor necrosis factor-alpha content in rat sciatic nerve after chronic constriction injury. Exp Neurol, 3,5. (scientific article)
- Sommer C..
(2001). Zytokine bei neuropathischen Schmerzen.. Anaesthesist, (scientific article)
- Sommer C, Schäfers M, Marziniak M, Toyka KV.
(2001). Etanercept reduces hyperalgesia in experimental painful neuropathy. J Peripher Nerv Syst, 1,3. (scientific article)
- Samsam M, Frei R, Marziniak M, Martini R, Sommer C.
(2002). Impaired sensory function in heterozygous P0 knockout mice is associated with nodal changes in sensory nerves. J Neurosci Res, 3,4. (scientific article)
- Schäfers M, Geis C, Brors D, Yaksh TL, Sommer C.
(2002). Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. J Neurosci, 8,2. (scientific article)
- Vogel C, Lindenlaub T, Tiegs G, Toyka KV, Sommer C.
(2000). Pain related behavior in TNF-receptor deficient mice. In Progress in Pain Research and Management Vol. 16 . IASP press. (conference publication)
- Sommer C.
(2001). Cytokines and neuropathic pain. IASP press. (Sonstiges)
