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.
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.
Authors: Stuart M Brierley; Patrick A Hughes; Amanda J Page; Kelvin Y Kwan; Christopher M Martin; Tracey A O'Donnell; Nicole J Cooper; Andrea M Harrington; Birgit Adam; Tobias Liebregts; Gerald Holtmann; David P Corey; Grigori Y Rychkov; L Ashley Blackshaw Journal: Gastroenterology Date: 2009-07-24 Impact factor: 22.682
Authors: Matt Petrus; Andrea M Peier; Michael Bandell; Sun Wook Hwang; Truc Huynh; Nicholas Olney; Tim Jegla; Ardem Patapoutian Journal: Mol Pain Date: 2007-12-17 Impact factor: 3.395
Authors: Jin Y Ro; Youping Zhang; Christina Tricou; Dan Yang; Joyce T da Silva; Ruixin Zhang Journal: J Gerontol A Biol Sci Med Sci Date: 2020-07-13 Impact factor: 6.053
Authors: James J Miller; Kazuhiro Aoki; Francie Moehring; Carly A Murphy; Crystal L O'Hara; Michael Tiemeyer; Cheryl L Stucky; Nancy M Dahms Journal: JCI Insight Date: 2018-03-22