Innate immune response may warn of chronic multisite musculoskeletal pain

An enhanced innate immune response may be an indicator of the onset or prolongation of chronic, multisite musculoskeletal pain, cross-sectional study findings suggest.

The study researchers found that 307 patients with chronic, multisite musculoskeletal pain had significantly higher levels of a number of lipopolysaccharide (LPS)-stimulated pro-inflammatory cytokines than 400 individuals without such pain after taking into account lifestyle and disease variables.

This finding indicates an enhanced innate immune response, which the researchers say may “reflect a disposition to respond with pro-inflammatory cytokines that may induce central sensitization and contribute to pain hypersensitivity.”

Mean levels of basal inflammatory markers were also significantly higher in chronic pain patients than controls, but significance was lost after adjustment for sociodemographical, lifestyle and disease variables, with body mass index and the number of chronic diseases having the largest effects.

“Our study suggests that obesity may contribute to a mild inflammatory state in chronic pain”, notes the team in Pain. “Therefore, a healthy lifestyle that reduces overweight may potentially decrease inflammatory levels in patients with chronic pain.”

The chronic pain patients had a Chronic Pain Grade of I to IV affecting the extremities as well as the back and neck, whereas controls had grade I pain in at most two locations.

Of 13 LPS-stimulated inflammatory markers studied, three remained significantly higher in chronic pain patients than controls, after accounting for confounders.

These were interleukin-2 (8.50 vs 7.61 pg/mL), tumour necrosis factor-β (327.7 vs 296.7 pg/mL) and matrix metalloproteinase-2 (72.83 vs 69.61 ng/mL).

There was no significant association between basal or LPS inflammatory makers and the severity of pain endured by the patients, however.

This suggests that “if subjects are sensitized to chronic pain, the increased activity of the immune system does not further amplify pain severity”, say the researchers, led by Ellen Generaal (VU University Medical Center, Amsterdam, the Netherlands).

They conclude: “Our findings suggest that the innate immune response could be examined as a potential biomarker for the onset and perpetuation of chronic pain.”

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