The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation.
This study investigated the role of TRPA1 in the development and maintenance of mechanical and cold hyperalgesia in persistent inflammation induced by Complete Freund's Adjuvant (CFA) in mice. The intraplantar (i.pl.) injection of CFA induced a long lasting (28 days) hyperalgesia for both mechanical and thermal (cold) stimuli. The intraperitoneal (i.p., 30-300 mg/kg), intraplantar (i.pl., 100 microg/site) or intrathecal (i.t., 10 microg/site) injection of the TRPA1 selective antagonist HC-030031 significantly reduced the mechanical hyperalgesia evaluated by the von Frey hair test. The effect of HC-030031 was evidenced on the day after CFA injection and was kept throughout the test. However, the intracerebroventricular (i.c.v., 10 microg/site) injection of HC-030031 did not interfere with CFA-induced hyperalgesia. Treatment with HC-030031 (300 mg/kg, i.p.) completely inhibited the noxious cold hyperalgesia induced by tetrafluoroethane in mice that received CFA. The pre-treatment with the TRPA1 oligonucleotide antisense (AS-ODN, i.t.) consistently prevented both mechanical and cold hyperalgesia. Interestingly, both TRPA1 protein expression and mRNA were over-expressed in spinal cord and dorsal root ganglia (DRG) of mice treated with CFA, an effect that was fully prevented by the pre-treatment with the TRPA1 antagonist HC-030031. Collectively, the present results showed that TRPA1 present at either peripheral or spinal sites play a relevant role in the development and maintenance of both mechanical and cold hyperalgesia during CFA-induced inflammation. Thus, TRPA1 selective antagonists represent promising candidates to treat hyperalgesia in persistent inflammatory states.
da Costa
Diogo Santos M
DSM
Departament of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil Departament of Chemistry, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Meotti
Flavia Carla
FC
Andrade
Edinéia Lemos
EL
Leal
Paulo César
PC
Motta
Emerson Marcelo
EM
Calixto
João B
JB
D000178:Acrylamides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D008297:Male; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology / Q000627:therapeutic use; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
C500530:3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo(b)(1,4)dioxin-6-yl)acrylamide; D000178:Acrylamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D005620:Freund's Adjuvant