Abstract
BackgroundThe 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.MethodsWe 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).ResultsWe 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.ConclusionsOur 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: DRKS00005954Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0225-0) contains supplementary material, which is available to authorized users.
Highlights
The classification of pain into nociceptive and neuropathic pain is based on characteristic symptoms and different pathophysiological mechanisms
IL-23 is a key cytokine in the control of inflammation in peripheral tissues, which stimulates naïve CD4 T-cells to differentiate into TH17 cells, in conjunction with IL-6 and Transforming growth factor-β (TGF-β)
Regulatory Tcell (Treg) have an antiinflammatory role by releasing anti-inflammatory cytokines like IL-10 and TGF-β
Summary
The classification of pain into nociceptive and neuropathic pain is based on characteristic symptoms and different pathophysiological mechanisms. In contrast to nociceptive pain, which is caused by damage or potential damage to tissue, neuropathic pain occurs due to a lesion or disease of the peripheral or central nervous system. It is characterized by burning and lancinating pain sensations and further somatosensory disturbances like hypo- and hypersensitivity. Comparable results were obtained by increasing the anti-inflammatory cytokines IL-4, IL-10 or Transforming growth factor-β (TGF-β) [10,11,12] Despite those promising experimental findings, there are no pharmacological agents available for the specific immunological therapy of neuropathic pain until now
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