Abstract
Patients: Patients suffering from dry mouth often complain of tongue pain. In this study, we elucidated the profile of phosphorylation of extracellular signal-regulated kinase （ERK） in trigeminal spinal subnucleus caudalis （Vc） neurons of the dry-tongue model rat in response to cold stimuli.
Methods: The dry-tongue model rats were developed by receiving tongue exposure in the dry air for 2 hr per day for 1-14 days under light anesthesia （2% isoflurane）. The nocifensive behavior to cold stimulation and phosphorylation of ERK in the Vc were compared between sham and dry-tongue model rats. In addition, we evaluated effects of continuous intrathecal （i.t.） administration of MEK inhibitor PD98059 on the nocifensive behavior and expression of pERK immunoreactive （IR） cells in Vc.
Results: Head-withdrawal threshold （HWT） to cold stimulation of the tongue significantly decreased on day 7 compared to sham rats （dry tongue model, 3.27±1.12℃; sham, −3.39±0.58℃）. The number of pERK-IR cells in the Vc significantly increased in comparison to that of sham rats on day 7 （dry tongue model, 41.2±3.6; sham; 23.0±3.6）. The decrement in the cold HWT were blocked by PD98059 （PD98059, −3.5±0.3℃; Vehicle, 3.2±0.4℃. In addition, PD98059 blocked an increase in the number of pERK-IR cells （PD98059, 27.6 ± 2.7; Vehicle; 39.1 ± 3.1）.
Conclusions: The present study demonstrated that cold hyperalgesia occurs in the dry-tongue rats and suggested that cold tongue pain in the dry-tongue model rats correlates with ERK phosphorylation in Vc neurons.
