Depression, cytokines and experimental pain: evidence for sex-related association patterns

There is robust evidence that altered neural-immune interactions including increased levels of proinflammatory cytokines are involved in both the pathogenesis of depression and altered pain processing. Proinflammatory cytokines induce sickness behavior, a constellation of symptoms that bears a strong similarity to those of depression. A feature of sickness behavior is enhanced pain sensitivity and it has been suggested that proinflammatory cytokines interact with pain processing directly and via several neurobiological pathways. Previous research indicates that depression and pain are closely related. We investigated the association between proinflammatory cytokines and experimental pain in major depression.

Psychopathological variables, pressure pain thresholds (PPT) and concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured in 37 outpatients with major depression and 48 healthy controls.

Compared with controls, depressed patients exhibited significantly higher levels of TNF-α and significantly decreased PPT indicating enhanced pain sensitivity. The group differences were robust when adjusting for sex and body mass index, although sex was significantly related to PPT. No group difference was observed in IL-6. PPT correlated significantly with TNF-α in women but not in men.

Because of the cross-sectional design, causality of the relation between TNF-α and pain cannot be determined. Results should be considered preliminary given the small sample size.

The present findings suggest that increased pain sensitivity in depression may be linked to increased TNF-α concentration. The absence of this association in men is discussed in terms of pain-related psychobiological sex differences.