When older relatives complain about pain, a little empathy is warranted. New preliminary research from University of Florida Health suggests that as people age, their bodies may respond to painful events with faster, stronger and longer-lasting inflammation than younger adults.
The study indicates that older adults could be more vulnerable to developing persistent pain after injuries or procedures. Researchers found that, following experimentally induced pain, levels of pro-inflammatory proteins rose higher and stayed elevated longer in older participants. Anti-inflammatory cytokines, which help calm inflammation, also appeared later in older adults than in younger ones. The results were reported in the journal Experimental Gerontology.
“Older people go through painful procedures more often, and we wanted to research whether this accumulation of painful procedures or more acute pain episodes that older people encounter is bad,” said Yenisel Cruz-Almeida, Ph.D., MSPH, an assistant professor in the UF College of Medicine’s department of aging and geriatric research and an affiliate of the UF Institute on Aging. “If you have enough of those in a shorter period of time, does this predispose you to have chronic pain?”
Joseph Riley, Ph.D., the study’s senior author and director of the pain clinical research unit at the UF Pain Research and Intervention Center of Excellence, explained that an amplified inflammatory response in older adults is likely to produce more pain signals from peripheral tissues — the limbs and tissues outside the spinal cord and brain. “If older adults are more likely to have these pain messages sent through the spinal cord to the brain, and the nervous system is being adapted to go through these changes, they may become more pain prone,” Riley said.
Although the research does not prove that repeated acute pain causes chronic pain in older adults, the findings support that possibility and represent an important first step in clarifying how aging changes the relationship between the immune system and pain. The researchers acknowledge the study’s small sample size but note that the differences between younger and older groups were large and consistent enough to suggest true age-related differences in inflammatory response.
Cruz-Almeida and Riley tested eight healthy older adults (average age 68) and nine healthy younger adults (average age 21). None of the participants had chronic conditions such as diabetes or hypertension. Pain was produced experimentally using two well-validated models: focal heat applied to the feet and a cold pressor task (immersion in cold water). During an initial visit, investigators determined each participant’s pain sensitivity to set a reproducible, tolerable intensity for subsequent sessions.
Participants rated their discomfort on a scale from 1 to 10. The research team aimed for a moderate pain level (about a 4) to create consistent stimuli while ensuring participants would complete later visits. To measure inflammatory activity, researchers placed an indwelling catheter to collect blood samples before and at 3, 15, 30, 45, 60 and 90 minutes after each pain stimulus. Analysis focused on inflammatory markers — pro-inflammatory cytokines such as TNF-α, IL-6 and IL-8, and anti-inflammatory cytokines including IL-4, IL-5 and IL-10.
Across both pain models, pro-inflammatory cytokines rose in both age groups but showed larger elevations in older adults for TNF-α and IL-8; IL-6 increased more in older adults after the cold pressor task. Anti-inflammatory cytokines tended to peak later in the older group and showed greater elevations in response to focal heat pain but not to the cold stimulus. These patterns are consistent with age-related alterations in immune regulation that may help explain why older adults experience more frequent or prolonged pain.
Riley emphasized that immune activation and inflammation are not inherently harmful — these responses are part of normal healing. However, he and Cruz-Almeida cautioned that prolonged immune activation may disturb the body’s balance and contribute to age-related conditions. “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,” Cruz-Almeida said. She added that low-grade, prolonged inflammation has been linked to metabolic and cardiovascular problems, though more research is needed to determine direct implications for chronic pain.
For patients and clinicians, one immediate implication may be the benefit of timely anti-inflammatory treatment after injury. “Early treatment of an injury even with over-the-counter anti-inflammatories may be a good idea,” Riley said. “It’s those first few days of bombarding the central nervous system with pain signals that has a bigger effect [on the body].”
Source: Morgan Sherburne, University of Florida
Image Credit: The image is in the public domain
Original Research: Abstract for “Age differences in cytokine expression under conditions of health using experimental pain models” by Yenisel Cruz-Almeida, Maria Aguirre, Heather L. Sorenson, Patrick Tighe, Shannon M. Wallet, and Joseph L. Riley III in Experimental Gerontology. Published online May 2016. doi:10.1016/j.exger.2015.09.017
Abstract
Age differences in cytokine expression under conditions of health using experimental pain models
Older adults face a higher risk of frequent and prolonged pain, and emerging evidence links immune system changes to pain susceptibility. This study tested whether healthy older adults exhibit larger immune responses to experimental pain than younger adults. Eight younger and nine older participants completed three sessions using validated human pain models: the cold pressor task (CPT), focal heat pain (FHP), and a non-painful thermal control. Blood was collected at baseline and at 3, 15, 30, 45, 60, and 90 minutes after stimuli. Pro-inflammatory cytokines (TNF-α, IL-6 and IL-8) peaked at similar time points for both groups but rose to greater levels in older adults for TNF-α and IL-8 in both pain models, and IL-6 following CPT. Anti-inflammatory cytokines (IL-4, IL-5, IL-10) generally peaked later among older participants, with larger elevations after FHP but not CPT. These findings support the view that age-related immune dysregulation may contribute to the increased prevalence and persistence of pain in older adults.
“Age differences in cytokine expression under conditions of health using experimental pain models” by Yenisel Cruz-Almeida et al., Experimental Gerontology. Published online May 2016. doi:10.1016/j.exger.2015.09.017