TY - JOUR
T1 - Effects of neutralizing antibodies to TNF-alpha on pain-related behavior and nerve regeneration in mice with chronic constriction injury
AU - Lindenlaub, Thies
AU - Teuteberg, Philipp
AU - Hartung, Thomas
AU - Sommer, Claudia
N1 - Funding Information:
We are grateful to Barbara Dekant and Lydia Biko for expert technical assistance. We thank K.V. Toyka for his contributions in the planning process and for helpful suggestions during the preparation of the manuscript. TL was supported by the Deutsche Forschungsgemeinschaft, SFB 353, the project was supported by Volkswagen-Stiftung.
PY - 2000/6/2
Y1 - 2000/6/2
N2 - Inhibition of proinflammatory cytokines reduces hyperalgesia in animal models of painful neuropathy. We set out to investigate the consequences of this treatment for nerve regeneration. Here we examined the sequels of epineurial application of neutralizing antibodies to tumor necrosis factor-alpha (TNF) in chronic constriction injury (CCI) of the sciatic nerve in C57/BL 6 mice. The mice were tested behaviorally for manifestations of thermal hyperalgesia and mechanical allodynia. Nerve regeneration was assessed by morphometry of myelinated nerve fibers in the sciatic nerve and of the epidermal innervation density in the glabrous skin of the hindpaws. Antibodies to TNF reduced thermal hyperalgesia and mechanical allodynia after CCI. Myelinated fiber density in the sciatic nerve was reduced to 30% of normal on day 7 after surgery, and reached 60% on day 45, with no difference between antibody-treated and untreated animals. Epidermal innervation density as shown by PGP 9.5 and CGRP immunohistochemistry was reduced to 25-47% at both time points after CCI, again without differences between antibody treated and untreated mice. Myelinated fiber density but not epidermal innervation density was correlated to thermal and mechanical withdrawal thresholds. We conclude that neutralization of endoneurial TNF attenuates pain related behavior but has no effect on nerve regeneration. Furthermore, the number of epidermal nerve fibers is not relevant to the magnitude of behavioral hyperalgesia in CCI. Copyright (C) 2000 Elsevier Science B.V.
AB - Inhibition of proinflammatory cytokines reduces hyperalgesia in animal models of painful neuropathy. We set out to investigate the consequences of this treatment for nerve regeneration. Here we examined the sequels of epineurial application of neutralizing antibodies to tumor necrosis factor-alpha (TNF) in chronic constriction injury (CCI) of the sciatic nerve in C57/BL 6 mice. The mice were tested behaviorally for manifestations of thermal hyperalgesia and mechanical allodynia. Nerve regeneration was assessed by morphometry of myelinated nerve fibers in the sciatic nerve and of the epidermal innervation density in the glabrous skin of the hindpaws. Antibodies to TNF reduced thermal hyperalgesia and mechanical allodynia after CCI. Myelinated fiber density in the sciatic nerve was reduced to 30% of normal on day 7 after surgery, and reached 60% on day 45, with no difference between antibody-treated and untreated animals. Epidermal innervation density as shown by PGP 9.5 and CGRP immunohistochemistry was reduced to 25-47% at both time points after CCI, again without differences between antibody treated and untreated mice. Myelinated fiber density but not epidermal innervation density was correlated to thermal and mechanical withdrawal thresholds. We conclude that neutralization of endoneurial TNF attenuates pain related behavior but has no effect on nerve regeneration. Furthermore, the number of epidermal nerve fibers is not relevant to the magnitude of behavioral hyperalgesia in CCI. Copyright (C) 2000 Elsevier Science B.V.
KW - Calcitonin gene related peptide
KW - Chronic constriction injury
KW - Epidermal innervation
KW - Nerve regeneration
KW - Protein gene product 9.5
KW - Tumor necrosis factor
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U2 - 10.1016/S0006-8993(00)02190-9
DO - 10.1016/S0006-8993(00)02190-9
M3 - Article
C2 - 10825476
AN - SCOPUS:0034595723
VL - 866
SP - 15
EP - 22
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -