Differential expression of cytokines in painful and painless neuropathies.
BACKGROUND
Pain is a common symptom in peripheral neuropathies. The factors determining why some peripheral neuropathies are painful and others are not are incompletely understood. Pro-inflammatory cytokines have been implicated to play a crucial role in the generation of pain.


OBJECTIVE
To investigate whether cytokine profiles differ between patients with painful or painless neuropathy.


METHODS
In this prospective study, we analyzed blood mRNA and protein levels of the pro-inflammatory cytokines interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF) and the anti-inflammatory cytokines IL-4 and IL-10 in 32 patients with painful neuropathy, 20 patients with painless neuropathy, and 38 healthy control subjects, using quantitative real-time PCR and ELISA.


RESULTS
Patients with a painful neuropathy had about twofold higher IL-2 mRNA (p = 0.001) and TNF mRNA (p < 0.0001) and protein levels (p = 0.009) than healthy control subjects and about twofold higher IL-2 and TNF mRNA (p = 0.03; p = 0.001) and protein levels (p = 0.04; p = 0.04) than patients with painless neuropathy. In contrast, mRNA levels of the anti-inflammatory cytokine IL-10 were about twofold higher in patients with painless neuropathy than in patients with painful neuropathy (p = 0.001) and controls (p = 0.004). IL-4 protein levels were 20-fold higher in patients with painless neuropathy (p < 0.0001) and 17-fold higher in patients with painful neuropathy (p < 0.0001) than in healthy control subjects.


CONCLUSIONS
A pro-inflammatory cytokine profile seems to be associated with pain in the setting of a peripheral neuropathy, corroborating findings in animal models with experimental painful neuropathies. This may have implications for future treatment strategies.
Uçeyler
Nurcan
N
Department of Neurology, University of Würzburg, Würzburg, Germany. ueceyler_n@klinik.uni-wuerzburg.de
Rogausch
Jan P
JP
Toyka
Klaus V
KV
Sommer
Claudia
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use; D015415:Biomarkers; D015897:Comorbidity; D003199:Computer Systems; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D003863:Depression / Q000150:complications; D004198:Disease Susceptibility; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000097:blood* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D010147:Pain Measurement; D010523:Peripheral Nervous System Diseases / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics
D000700:Analgesics; D015415:Biomarkers; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4