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.