Older adults are at an increased risk to develop frequent and prolonged pain. Emerging evidence proposes a link between immune changes and pain, which is consistent with the inflammation theory of aging and the increased incidence of age-related diseases. This study tested the hypothesis that older adults show greater immune responses to experimental pain compared to younger individuals. Study subjects (8 younger and 9 older healthy adults) underwent 3 experimental sessions using well-validated human experimental pain models: the cold pressor task (CPT), focal heat pain (FHP), and a non-painful thermal control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, 60, and 90 minutes post-stimuli administration. Pro-inflammatory cytokines (TNF-α IL-6 and IL-8) peaked at the same time points for both groups, with greater elevations among older subjects for TNF-α and IL-8 in both pain models and elevations in IL-6 only for CPT. Antiinflammatory cytokines (IL-4, IL-5, and IL-10) generally peaked later for the older subjects, with increased elevations for FHP but not the CPT. These data is consistent with the assertion that agerelated immune system dysregulation may account for the increased prevalence of pain in older adults.

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An important consideration in mechanistic research using biomarkers should include the use of saliva as an alternative to blood. The use of saliva would allow the study of susceptible populations such as older adults where venipuncture may not be feasible. Although saliva has been most commonly used to measure cortisol and tumor necrosis factor-α (TNFα), there is limited evidence that other cytokines found in saliva significantly change in response to laboratory-induced pain. Therefore, the aim of the current preliminary study was to characterize the time course, duration and magnitude of changes of commonly measured pro- (interleukin [IL]-6, IL-8) and anti-inflammatory (IL-10, IL-4) cytokines in saliva samples and to test for age-related differences in separate experimental painful and non-painful control sessions. In addition, we also tested whether venipuncture results in significant cytokine alterations similar to a painful stimulus in a non-painful, non-venipuncture control session. All cytokines were significantly induced by the cold pressor task compared to a warm control session (p < 0.001). Specifically, healthy older adults experienced greater salivary changes in all cytokines during the cold pressor session compared to younger adults in the non-painful sessions (p < 0.001). There were no significant differences between the venipuncture and non-venipuncture sessions across all cytokines (p > 0.05). Our findings support the use of saliva as a substitute for blood in both young and older healthy individuals to measure changes after experimental pain stimulation. In addition, venipuncture alone is not sufficient to induce IL-6, IL-8, IL-10 and IL-4. Future studies in the community are urgently needed to validate and further move translational mechanistic pain research to those populations most underrepresented in clinical research.

This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), both in magnitude and time-course. Eight younger and 9 older adults underwent 3 experimental sessions using well-validated laboratory pain models: cold pressor task (CPT), contact heat pain (HP), and a non-painful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60-minutes post-stimuli administration. Older adults had higher baseline levels of both neuropeptides suggesting increased peripheral activity compared to younger adults. Following CPT, older adults demonstrated a quick and strong release of substance P with dramatic recovery, whereas young adults maintained a constant low-grade response. Unlike substance P, β-endorphin increased between 3 and 15 minutes for both groups with the upsurge substantially higher for older adults. Following HP, younger adults had an immediate surge in circulating substance P and β-endorphin that was more pronounced than among older adults. However, levels of substance P for younger adults slowly tapered whereas they continued to climb for the older adults through 30 minutes. β-endorphin peaked at 30 minutes for both groups and returned to baseline. No changes were observed during the non-painful control.

perioperative outcomes were similar according to presence/absence of erectile dysfunction. Patients with erectile dysfunction were a significant increase in latency of pudendal nerve SSEP (19.4 vs 16.9 ms, p¼0.001). Patients with postoperative incontinence (PPI) were a significant increase in latency of pudendal nerve SSEP (19.5 vs 17.9 ms, p¼0.014).CONCLUSIONS: Our results suggest that pudendal nerve SSEP can be an effective tool in the evaluation of patients with PPI and erectile dysfunction. The test can be used to provide more definitive assessment of functional dysfunction.