title: Nociceptor Sensitization Depends on Age and Pain Chronicity(1,2,3).
abstract: 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 the greater burden of chronic pain 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 old) and aged (>18 months old) 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 twofold mechanical sensitization in C fibers during acute inflammation, but an unexpected twofold reduction in firing during chronic inflammation. Responsiveness to capsaicin and mechanical responsiveness of A-mechanonociceptor (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 with controls during either the acute or chronic inflammatory phases, despite strong behavioral sensitization to mechanical stimuli at these time points. These results reveal the following 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.
authors: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors: Andy D
authors: 0000-0003-4485-9530
authors: AD
authors: Weyer
authors: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors: Katherine J
authors: 0000-0002-4419-4834
authors: KJ
authors: Zappia
authors: Promentis Pharmaceuticals , Milwaukee, Wisconsin 53203.
authors: Sheldon R
authors: 0000-0003-0745-629X
authors: SR
authors: Garrison
authors: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors: Crystal L
authors: 0000-0002-0868-2582
authors: CL
authors: O'Hara
authors: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors: Amanda K
authors: AK
authors: Dodge
authors: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin , Milwaukee, Wisconsin 53226.
authors: Cheryl L
authors: 0000-0003-4966-6594
authors: CL
authors: Stucky
mesh_terms: D000200:Action Potentials; D000375:Aging; D000818:Animals; D059333:Central Nervous System Sensitization; D002908:Chronic Disease; D005620:Freund's Adjuvant; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D059225:Nociception / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000150:complications / Q000503:physiopathology*; D017288:Pain Threshold
chemical_list: D005620:Freund's Adjuvant
keywords: acute pain; aging; chronic pain; mechanical; sensitization; skin–nerve preparation