Kontakt

Prof. Dr. med.
Siegfried Mense


Center for Biodmedicine
and Medical Technology
Mannheim
Medical Faculty Mannheim
of the University of
Heidelberg
68167 Mannheim
Tel. +49 621 383-9713
Fax: +49 621 383-9949
Email


Prof. Dr. Siegfried Mense

MD 1989 University of Bonn,

Assistant Professor at the University of North Carolina

at Chapel Hill, USA, 1978-1979,

Professor at the Department of Anatomy and Cell Biology, IZN, University of Heidelberg, since 1985.

Current Research

Muscle pain

In experimental animals in vivo, a painful lesion of skeletal muscle leads to marked neuroplastic changes in primary afferent fibres (PAFs) and in the spinal cord. The changes consisted (among others) of increased synthesis and release of NGF and neuropeptides (SP and CGRP) in PAFs, increased expression of FGF2 in astrocytes, electrical hyperexcitability of dorsal horn neurones, and altered expression of nitric oxide synthase (NOS) in neurones in the dorsal horn and substantia intermedia. Collectively, these changes reflect a lesion-induced functional reorganisation of the dorsal horn.

In contrast to most of the lesion-induced changes which lead to hyperexcitability of dorsal horn neurones, FGF2 had a depressive action on the discharge activity when adminstered iontophoretically close to the cells. This finding shows that besides its well-known neurotrophic actions, FGF2 has also an effect on the electrical acticity of spinal neurones.

During chronic muscle lesions such as a myositis, the changes in NOS expression (reflected in the number of NOS-immunoreactive (ir) or diaphorase-positive neurones) showed a bidirectional time-course with an initial increase followed by a decrease. The time-constant of the time-course depended largely on the frequency of the discharges in primary afferent C fibres: the higher the frequency, the faster the time-course. The transient increase in NOS-IR was associated with enhanced expression of NOSmRNA as shown with in situ hybridisation. In our animal model (anaesthetised rats), a local lack of NO induced by blocking the spinal NOS with topically applied L-NAME had a strong excitatory action on the discharges of nociceptive dorsal horn neurones.

Normally, NO appears to be tonicly released in the spinal cord and inhibits the activity of nociceptive neurones. When NO synthesis is blocked, the neurones are disinhibited. This finding contrasts with most of the published data on the spinal function of NO, which is generally assumed to have a pro-nociceptive (hyperalgesia-inducing) action.

Spinal cord injury

The pain of patients with spinal cord injury (SCI) is a clinical problem, because the commonly used analgesics (including morphine) are largely ineffective. Therefore, an animal model for SCI pain is needed to test novel analgetic therapies.
Six weeks after a transection of the thoracic spinal cord, rats exhibit hyperactivity of the urinary bladder (reflex bladder), spasms of the hindlimb muscles and signs of hyperalgesia in the dermatomes close to the segment of the lesion. One of the immunohistochemical changes observed in these animals is a reduction in the number of NOS-ir neurones in the segments directly rostral to the lesion. The associated lowering of spinal NO concentration is likely to lead to increased activity in nociceptive cells (see above) and, therefore, to spontaneous pain in conscious individuals.

Future Projects and Goals

Muscle Pain

Electrically induced activity in C fibres from muscle is much less effective in driving dorsal horn neurones than is activity in C fibres from the skin, even though discharges in muscle C fibres reportedly have a stronger action with regard to the induction of neuroplastic changes. Because the connectivity of muscle C fibres in the dorsal horn is unknown, one of the future projects aims at clarifying the location of synapses of muscle C fibres on dorsal horn neurones.

Another aim is to study the spinal effects of input via tetrodoxin-resistant C fibres from muscle on these cells.

Spinal cord injury

Future experiments will focus on the recording of discharges from dorsal horn neurones in animals with SCI, and on influencing their activity with L-arginine (the substrate of NOS) and other substances (e.g. NK1-receptor antagonists).

The mechanisms underlying the reduction of the number of NOS-ir dorsal horn cells in SCI animals (e.g., downregulation, apoptosis, necrosis) will also be addressed.

Selected publications

[1] Reinert, A., Kaske, A., and Mense, S. (1998) Inflammation-induced increase in the density of neuropeptide-immunoreactive nerve endings in rat skeletal muscle. Exp. Brain Res. 121, 174-180.

[2] Callsen-Cencic, P. and Mense, S. (1999) Increased spinal expression of c-Fos following stimulation of the lower urinary tract in chronic spinal cord-injured rats. Histochem. Cell Biol. 112, 63-72.

[3] Callsen-Cencic, P. and Mense, S. (1999) Mechanisms underlying the pathogenesis of urinary bladder instability - new perspectives for the treatment of reflex incontinence. Restor. Neurol. Neurosci. 14, 115-126.

[4] Hoheisel, U., Unger, T., and Mense, S. (2000) A block of spinal nitric oxide leads to increased background activity predominantly in nociceptive dorsal horn neurones in the rat. Pain, 88, 249-257

[5] Schomburg, E.D., Steffens, H., Mense, S. (2000) Contribution of TTX-resistant C-fibres and A?-fibres to nociceptive flexor-reflex and non-flexor-reflex-pathways in cats. Neuroscience Res. 37, 277-287

Verantwortlich: E-Mail,   Letzte Änderung: Tue, 13.09.2016
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