BACKGROUND: The classification of pain into nociceptive and neuropathic pain is 
based on characteristic symptoms and different pathophysiological mechanisms. In 
a recent investigation, we found a disrupted TH17/Treg balance in patients 
suffering from chronic unspecific low back pain (CLBP). These patients did not 
show any signs of neuropathy. There is evidence for a considerable impact of the 
immune system also in neuropathic pain. However, the role of the adaptive immune 
system is still unclear. In the present study, we investigated systemic T-cell 
subset responses and T-cell related cytokine profiles in patients with chronic 
neuropathic pain.
METHODS: We analyzed T-cell subsets, mRNA expression and T-cell-related cytokine 
profiles in 26 patients suffering from neuropathic pain in comparison to 26 
healthy controls. Using multicolor flow cytometry (FACS), we quantified the 
number of T helper cells 1 (TH1), TH2, TH17 and regulatory T-cells (Tregs). 
Forkhead-Box-Protein 3 (FoxP3), Transforming growth factor-β (TGF-β) and 
RAR-related orphan receptor-γT (ROR-γT) mRNA expression was determined by 
quantitative real-time PCR (qPCR) and levels of pain-related cytokines were 
measured by Human Cytokine Multiplex Immunoassay (Macrophage inflammatory 
protein-1α (MIP-1α), Tumor necrosis factor-α (TNF-α), Interferon-γ (IFN-γ), 
Interleukin (IL) -4, IL-6, IL-10, IL-17, and IL-23).
RESULTS: We found a TH17/Treg imbalance with significantly increased 
anti-inflammatory Tregs and decreased pro-inflammatory TH17 cells in patients 
with neuropathic pain as compared to healthy controls. These results were 
confirmed on mRNA level: Treg-related FoxP3 and TGF-β mRNA expression was 
elevated, whereas expression of TH17-related RORγT was reduced. Cytokine 
analyses revealed only marginal changes.
CONCLUSIONS: Our investigation revealed a clear shift of T-cell subsets towards 
anti-inflammation in patients with neuropathic pain. Interestingly, this is 
quite similar to our previous findings in CLBP patients, but even more 
pronounced. Therefore, it remains to be elucidated in future investigations 
whether the immune changes represent an underlying pathophysiological mechanism 
or an epiphenomenon induced by ongoing pain and stress.
GERMAN CLINICAL TRIAL REGISTER (DRKS): Trial registration number: DRKS00005954.