Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients

Objective: Inflammatory cytokines as well as nitric oxide (NO) play a key role in the pathogenesis of persistent and exaggerated pain states. To document this, we investigated whether a range of cytokines and NO were detectable in the plasma of chronic pain patients and whether cytokine and NO levels correlated with pain severity. Methods: Plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained. Average pain intensity during the last 24h was assessed on a 11-point numeric rating scale and patients were distributed to three groups: light, moderate and severe pain. The concentrations of TNF-α, GM-CSF, interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, IL-2, IL-4, IL-5, IL-10 and nitrate/nitrite were determined. Results: Patients with light pain demonstrated significantly increased levels of IL-6 compared to controls. In the severe pain group IL-6 and nitrate/nitrite were significantly increased. Serum concentrations of IL-1β, TNF-α, IL-2 and IL-4 were increased but as we adjusted the level of significance at p = 0.0045, most cytokine plasma levels failed to reach statistical significance. Conclusions: Pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IFN-γ, TNF-α) in the plasma correlate with increasing pain intensity. Chronic pain patients show a significant increase in plasma levels of NO in comparison to healthy controls.