Age, Inflammation and Transition From Acute to Chronic Pain

Caused by dysregulation of inflammatory responses

Researchers at the University of Florida recently investigated the role of inflammation and age in pain perception.1 Older adults are more likely to undergo procedures that incur periods of acute pain. The researchers postulated that accumulation of such events might predispose older patients to chronic pain as a result of prolonged and elevated inflammatory responses.

Subjects in 2 age groups (older adults, n=9, average age 68; and younger adults, n=8, average age 21) were exposed to experimental painful stimuli using the cold pressor task (CPT) and focal heat pain (FHP). For CPT, subjects were asked to immerse their foot in a cold water bath (8°C for men, 10°C for women). For FHP, a thermode delivered a heat stimulus (48°C for men, 47°C for women) to the subjects’ palm. In both tests, subjects were asked to rate their pain on a 1 to 10 scale.

Blood samples were collected at different time points following painful pain stimuli, up to 90 minutes, and compared to pre-stimulus baseline. Compared with younger adults, older subjects had higher levels of proinflammatory cytokines tumor necrosis factor- α (TNF-α) and interleukin-8 (IL-8) following both types of pain stimuli, and higher levels of IL-6 following CPT; cytokines followed a similar time course in both age groups. Time course of anti-inflammatory cytokine (IL-4, 5, 10) responses differed with age and peaked at a later time point in older subjects. Their levels were enhanced after FHP but not after CPT.

The authors concluded that observed discrepancies in immune response might account in part for higher prevalence of pain in older adults. If this theory proves correct in future studies, early administration of anti-inflammatory drugs following a painful procedure might prevent age-related transition from acute to chronic pain. Joseph Riley, PhD, director of the pain clinical research unit at the University of Florida’s Pain Research and Intervention Center of Excellence and the study’s senior author, affirmed that “early treatment of an injury even with over-the-counter anti-inflammatories may be a good idea.”

Results from this study do not establish that accumulation of acute pain experiences predisposes older adults to chronic pain, but investigators are looking to test this hypothesis in future studies. “We think that the longer you have the immune system activated, having these elevated inflammatory cytokines, the more this activation can alter the homeostasis of the body. Usually an imbalance like that can be associated with autoimmune disorders, which also increase with age,” Yenisel Cruz-Almeida, PhD, said in a statement. “But the truth is, we don’t know what the direct implications would be. We think low-grade inflammation is related to endocrine abnormalities such as diabetes and the development of heart problems. … We need to keep looking and doing future research.”


1. Cruz-Almeida Y, Aguirre M, Sorenson HL, Tighe P, Wallet SM, Riley JL. Age differences in cytokine expression under conditions of health using experimental pain models. Exp Gerontol. 2015;72:150-156 .

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