Third-party-funded project
Title:
Experimental studies on the influence of the local immune reaction on pain-associated behavior after nerve lesion: modification of the cytokine cascade
Project management at the University of Würzburg:
Participating scientists:
Abstract:
We investigated the link between cytokine inhibition, reduction of hyperalgesia and regeneration in painful neuropathies. Briefly, an early increase in TNF and a loss of IL-10 in the nerve were associated with the onset of pain related behavior in the animals. Blockade of TNF reduced hyperalgesia and blocked the reduction of IL-10. TNF-receptors, in paricular TNF-R2 were upregulated early and protractedly, proposing a potential therapeutic target. In the model of chronic constrictive nerve injury (CCI) used in our previous studies, the presence of a foreign body (ligatures) might be causal for the cytokine upregulation. We therefore established a new model, the ‚partial sciatic nerve transection' (PST) without the presence of a foreign body. This model leads to reproducable hyperalgesia, cytokine upregulation, and hyperalgesia can be reduced by cytokine blockade. Thus nerve lesion by itself and not the foreign body reaction are responsible for the pain associated behavior. Also, successful nerve regeneration was correlated with a decrease in hyperalgesia.
Key words:
Neuropathic pain
tumor necrosis factor-alpha
interleukin-10
partial sciatic nerve transection
Projekt period:
from 07.1998 to 07.2001
Funding institution:
VW-Stiftung ,Granting date: 25.02.1998
Publications:
- Sommer C.
(1999). Tierexperimentelle Untersuchungen bei neuropathischem Schmerz: die pathogene und therapeutische Bedeutung von Zytokinen und Zytokinrezeptoren. Schmerz, 0,6. (scientific article)
- Lindenlaub T, Sommer C.
(2000). Partial sciatic nerve transection as a model of neuropathic pain: a qualitative and quantitative neuropathological study. Pain, 4,5. (scientific article)
- George A, Marziniak M, Schäfers M, Toyka KV, Sommer C.
(2000). Thalidomide treatment in chronic constrictive neuropathy decreases endoneurial tumor necrosis factor-alpha, increases interleukin-10 and has long-term effects on spinal cord dorsal horn met-enkephalin. Pain, 4,5. (scientific article)
- Lindenlaub T, Teuteberg P, Hartung T, Sommer C.
(2000). Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury. Brain Res, 2,5. (scientific article)
- Sommer C, Lindenlaub T, Teuteberg P, Schäfers M, Hartung T, Toyka KV.
(2001). Anti-TNF-neutralizing antibodies reduce pain-related behavior in two different mouse models of painful mononeuropathy. Brain Res, 2,5. (scientific article)
- Schäfers M, Brinkhoff J, Neukirchen S, Marziniak M, Sommer C.
(2001). Combined epineurial therapy with neutralizing antibodies to tumor necrosis factor-alpha and interleukin-1 receptor has an additive effect in reducing neuropathic pain in mice. Neurosci Lett, 2,0. (scientific article)
- Lindenlaub T, Sommer C..
(2002). Epidermal innervation density after partial sciatic nerve lesion and pain related behavior in the rat. Acta Neuropathol, 2,1. (scientific article)
