Contribution of Transient Receptor Potential Ankyrin 1 to Chronic Pain in Aged Mice With Complete Freund's Adjuvant-Induced Arthritis

Autor: Sheldon R. Garrison, Cheryl L. Stucky
Rok vydání: 2014
Předmět:
Zdroj: Arthritis & Rheumatology. 66:2380-2390
ISSN: 2326-5191
DOI: 10.1002/art.38724
Popis: Objective To investigate age-related differences in mechanical sensitivity to inflammatory pain and determine the contribution of transient receptor potential ankyrin 1 (TRPA1) to mechanical hypersensitivity during chronic inflammation in young and aged mice with complete Freund's adjuvant (CFA)–induced arthritis. Methods Mechanical sensitivity in young (3-month-old) and aged (24-month-old) wild-type (TRPA1+/+) mice and TRPA1-deficient (TRPA1−/−) mice was measured behaviorally for 8 weeks following injection of CFA into the plantar hind paw. The severity of inflammation was evaluated by histologic analyses and hind-paw measurements. Ex vivo preparations of the skin saphenous nerve from mice were assessed for C-fiber sensitivity. Results Among naive (uninjured) wild-type mice, aged animals were less sensitive than young animals to mechanical stimuli. Afferent recordings of C-fibers from TRPA1−/− mice indicated that TRPA1 contributes to the normal mechanical sensitivity in both age groups. Following injection of CFA, both young and aged TRPA1+/+ mice exhibited mechanical hypersensitivity. In young TRPA1−/− mice injected with CFA, peak development of mechanical hypersensitivity was delayed until week 4, when they exhibited a sharp decrease (9-fold) in the mechanical paw withdrawal threshold, whereas aged TRPA1−/− mice did not exhibit mechanical hypersensitivity at any time during the 8 weeks after CFA injection. Recordings of C-fibers from the saphenous nerve supported these findings, with results indicating that both young and aged TRPA1+/+ mice exhibited increased action potential firing at 8 weeks after CFA injection (increases of 25% and 60%, respectively). Interestingly, among TRPA1−/− mice injected with CFA, mechanical firing was increased markedly in the C-fibers of young mice (increase of 80%) but not in the C-fibers of aged mice. Conclusion These findings reveal marked differences in the long-term mechanical behavioral sensitivity of aged and young mice, and suggest that TRPA1 may be a key contributor to the transition from acute to chronic inflammatory pain in response to mechanical stimuli as well as to the development of nociceptor sensitization selectively in aged mice.
Databáze: OpenAIRE
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