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

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.

Plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained. Average pain intensity during the last 24 h 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-alpha, GM-CSF, interleukin (IL)-1beta, IL-6, IL-8, interferon (IFN)-gamma, IL-2, IL-4, IL-5, IL-10 and nitrate/nitrite were determined.

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-1beta, TNF-alpha, 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.

Pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, TNF-alpha) 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.