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 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.

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-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.

Conclusions: 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.