RT Journal Article SR Electronic T1 Nociceptor sensitization depends on age and pain chronicity JF eneuro JO eneuro FD Society for Neuroscience SP ENEURO.0115-15.2015 DO 10.1523/ENEURO.0115-15.2015 A1 Andy D. Weyer A1 Katherine J. Zappia A1 Sheldon R. Garrison A1 Crystal L. O’Hara A1 Amanda K. Dodge A1 Cheryl L. Stucky YR 2016 UL http://www.eneuro.org/content/early/2016/01/08/ENEURO.0115-15.2015.abstract AB Peripheral inflammation causes mechanical pain behavior and increased action potential firing. However, most studies examine inflammatory pain at acute, rather than chronic time points, despite chronic pain’s greater burden on patient populations, especially aged individuals. Furthermore, there is disagreement in the field about whether primary afferents contribute to chronic pain. Therefore, we sought to evaluate the contribution of nociceptor activity to the generation of pain behaviors during the acute and chronic phases of inflammation in both young and aged mice. We found that both young (2 months) and aged (> 18 months) mice exhibited prominent pain behaviors during both acute (2-day) and chronic (8-week) inflammation. However, young mice exhibited greater behavioral sensitization to mechanical stimuli than their aged counterparts. Teased fiber recordings in young animals revealed a 2-fold mechanical sensitization in C fibers during acute inflammation, but an unexpected 2-fold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of AM fibers were also reduced chronically. Importantly, this lack of sensitization in afferent firing during chronic inflammation occurred even as these inflamed mice exhibited continued behavioral sensitization. Interestingly, C fibers from inflamed aged animals showed no change in mechanical firing compared to controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal two important findings: 1) nociceptor sensitization to mechanical stimulation depends on age and the chronicity of injury, and 2) maintenance of chronic inflammatory pain does not rely on enhanced peripheral drive.Significance Statement: Most peripheral pain research examines acute pain in young animals, with the assumption that peripheral pain mechanisms are similar during acute pain and chronic pain for animals of all ages. Our results indicate that peripheral nociceptors may contribute minimally to pain sensation at chronic inflammatory time points in young populations, and at either acute or chronic time points in aged populations. These findings have important implications for novel analgesic design, as drugs targeting peripheral pain mechanisms observed under acute inflammatory conditions may be unlikely to show efficacy under chronic inflammatory conditions. Additionally, since nociceptors from aged animals do not change their firing rates in response to acute or chronic pain, peripherally-acting analgesics may also be largely ineffective in aged populations.