Our study is limited by its retrospective design. Be cause the follow up schedu

The wild type mice spent only 1. 7 seconds licking, whereas the p35 mice licked for more than 13 seconds, indicating much lower pain sensation in the p35 mice, The number of attempts [You must be registered and logged in to see this link.] and the licking time decreased significantly in the case of the wild type mice over the entire test period. However, there were no changes in the licking patterns of the p35 mice after inducing the mild pain, and more obvious changes were observed inducing more painful conditions. In compar ing the wild type and the p35 mice, there were also clear changes in the licking pattern episodes caused by different nociceptive stimulation, Discussion The present study shows that Cdk5 has an important role in orofacial pain signaling, and that this kinase is associated with mechanical nociception in the mouse vibrissal pad.

We utilized two sets of mice with signifi cantly altered Cdk5 activity to confirm its association with orofacial pain. Both p35 knockout and transgenic p35 mice depicted an altered response towards the mechanical stimulation. When tested with mechanical stimuli, the mice lacking the p35 gene showed hypoalgesia, whereas the mice overexpressing p35 hyperalgesia. Thus, these results [You must be registered and logged in to see this link.] clearly establish a correlation between Cdk5 activity and mechanical nociception. Since the discovery of Cdk5, numerous studies have revealed its multifunctional roles in important physio logical processes, such as brain development and function, neuronal migration, synaptic plasticity, mem ory, learning, and neurodegenerative disease processes, Our previous studies demonstrated that p35, as well as Cdk5, are expressed in the dorsal root and the trigeminal ganglia, and that the expression and activity of Cdk5 p35 is increased during the inflamma tion.

We and others have also reported that Cdk5 is required for the basal responses to noxious heat, The p35 knockout mice showed delayed responses to the painful thermal stimulation whereas the mice [You must be registered and logged in to see this link.] overexpressing p35 were more sensitive to painful ther mal stimulation at the hind paws and tail. Moreover, the inhibition of Cdk5 activity in the cultured DRG neurons attenuates the capsaicin evoked calcium influx, thus in dicating a close link between Cdk5 and TRPV1, This link was further confirmed using the nociceptor specific Cdk5 conditional knockout mice, which developed thermal hypoalgesia associated with reduced phosphoryl ation of TRPV1, In the current study, we extended our analysis to the role of Cdk5 in orofacial pain.

There are several animal models for studying the dif ferent types of pain; whether acute or chronic. Despite this, there is still a paucity of animal models to study orofacial pain, especially in mice. The majority of the be havioral pain tests in the orofacial area are based on pain related spontaneous behavior. All these tests induce the pain by an injection of various chemicals into the upper lip or the vibrissal pad, and observe licking or grooming behavior.