TNF-alpha expression in painful and nonpainful neuropathies.
OBJECTIVE
To determine whether the cytokine tumor necrosis factor alpha (TNF-alpha) acts as a pain mediator in neuropathic pain in humans.


BACKGROUND
In animal models, inflammatory cytokines such as TNF-alpha have been shown to facilitate neuropathic pain.


METHODS
The expression of TNF-alpha was analyzed immunohistochemically in 20 human nerve biopsy specimens of patients with painful (n = 10) and nonpainful (n = 10) neuropathies. Additionally, serum soluble TNF-alpha receptor I (sTNF-RI) levels were determined in 24 patients with neuropathies, 16 of which were painful and 8 that were painless.


RESULTS
Colocalization studies by confocal fluorescence microscopy for S-100 and TNF-alpha showed expression of TNF-alpha in human Schwann cells. Patients with painful neuropathies showed a stronger TNF-alpha immunoreactivity in myelinating Schwann cells relative to the epineurial background staining compared with patients with nonpainful neuropathy (0.949 +/- 0.047 vs 1.010 +/- 0.053, p < 0.05). Although there was no difference in sTNF-RI levels between painful (n = 16) and nonpainful (n = 8) neuropathies (sTNF-RI: 1412 +/- 545 pg/mL vs 1,318 +/- 175 pg/mL), patients with a mechanical allodynia (n = 9) had elevated serum sTNF-RI (1627 +/- 645 pg/mL vs 1233 +/- 192 pg/mL, p < 0.05) compared with patients without allodynia (n = 15).


CONCLUSIONS
TNF-alpha expression of human Schwann cells may be up-regulated in painful neuropathies. The elevation of sTNF-RI in patients with centrally mediated mechanical allodynia suggests that systemic sTNF-RI levels may influence central pain processing mechanisms.
Empl
M
M
Neurobiology Laboratory, Department of Research and Clinical Neurology, University Hospital, Basel, Switzerland. moem@brain.nefo.uni-muenchen.de
Renaud
S
S
Erne
B
B
Fuhr
P
P
Straube
A
A
Schaeren-Wiemers
N
N
Steck
A J
AJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001706:Biopsy; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D010523:Peripheral Nervous System Diseases / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D001798:Blood Proteins; D014409:Tumor Necrosis Factor-alpha