title: Contribution of transient receptor potential ankyrin 1 to chronic pain in aged mice with complete Freund's adjuvant-induced arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.affiliation: Medical College of Wisconsin, Milwaukee.
authors.forename: Sheldon R
authors.initials: SR
authors.lastname: Garrison
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Stucky
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D059350:Chronic Pain / Q000139:chemically induced / Q000378:metabolism*; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010812:Physical Stimulation; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D005620:Freund's Adjuvant