The cooling compound icilin activates two thermosensitive transient receptor potential channels, TRPM8 and TRPA1. This study assessed the effect of icilin on responses of naïve or nerve-injured rats to orofacial noxious cold stimulation with tetrafluoroethane spray. The cold stimulus was applied to the center of the vibrissal pad and duration of facial grooming behavior was recorded over the first 2 min. Injected into the upper lip, icilin caused dose-dependent increases in duration of facial grooming behavior of naive rats at 30 min post injection (10.5 ± 1.7 s for vehicle; 25.4 ± 3.3 and 33.1 ± 3.6 s for 10 and 30 µg/50 µl of icilin, respectively). This response was not observed in neonatally capsaicin-treated animals (50 mg/kg). Rats injected with icilin (30 µg) on Day 1 were refractory to the hyperalgesic effect of subsequent injections of the drug on Days 4 and 10. To assess the effect of icilin in nerve-injured animals, two loose silk 4-0 ligatures were tied around the infraorbital nerve of anesthetized rats. The cold hyperalgesia seen on Day 4 after this procedure was potentiated by 117 and 132%, at 30 and 60 min after icilin injection, respectively. Local administration of the TRPV1/TRPM8 antagonist capsazepine (30 µg) prevented icilin-induced cold hyperalgesia and transiently reversed that induced by nerve injury. Thus, icilin sensitizes rats to orofacial noxious cold stimulation by acting on TRPA1 and/or TRPM8 channels located on capsaicin-sensitive C fibers. These results suggest that specific blockers of such channels might be an effective tool for cold hyperalgesia treatment.