Low blood levels of two anti-inflammatory proteins could be key to chronic pain, researchers report.

Low concentrations of two cytokines, IL-4 and IL-10, were found in patients with chronic widespread pain, according to a German study published in the August issue of Arthritis & Rheumatism.

Cytokines are proteins that act as messengers between cells.

The study included 40 patients who'd received intravenous immunoglobulin (IVIG) as a novel treatment for pain that hadn't responded to standard therapy and another 15 patients who did not receive IVIG. The study also included a control group of 40 healthy people.

Blood samples were collected from all the study volunteers, and the pain patients were asked to rate their pain, fatigue, mood and cognitive function.

Compared with the control group, the 40 pain patients had significantly lower levels of IL-4 and IL-10. The 15 patients in the second group had similar results, although the difference in their levels of IL-10 compared to people in the control group was not statistically significant.

Several factors may be involved in low levels of these cytokines and how they influence pain, the study authors said. They noted that previous studies have shown that IL-10 reduces sensitivity to pain and that IL-4 can also dull pain response.

Genetic variations in different cytokine genes are associated with certain diseases. For example, IL-4 gene variations are associated with asthma, Crohn's disease and chronic polyarthritis, the researchers said.

"The low levels of IL-4 and IL-10 we observed in the patients with chronic widespread pain might therefore also be caused by genetic alterations either in the cytokine genes themselves or in regulatory elements, although other factors may be involved," they explained.