These results demonstrate that the blockade of ERK phosphorylation in Vc and C1 C2 neurons partially depressed the development of CFA induced mechanical allodynia and heat hyperalgesia in the tongue. Lastly, i. t. administration of PD98059 also caused profound suppression of pERK expression in the ipsilateral Vc and C1 C2 on day 8 after CFA injection, whereas no change in the number of pERK selleck chem IR cells was observed following i. t. administration of PD98059 in the side contralateral to the CFA injection. Involvement of mGluR5 in ERK mediated inflammatory pain signaling To evaluate the hypothesis that metabotropic glutamate receptor 5 might act as an upstream activator mediator in ERK dependent inflammatory pain signaling, we next performed the double immunofluorescence la beling to identify the nature of mGluR5 IR cells following noxious mechanical stimulation of the tongue on day 8 after CFA injection.

Most mGluR5 IR cells showed NeuN immunoreactivity in Vc and C1 C2 and mGluR5 was expressed in a rim region of pERK IR cell bodies, indicating that ERK Inhibitors,Modulators,Libraries was phosphorylated in neurons in which mGluR5 was expressed. On day 8 after CFA injection, mGluR5 protein expression in Vc and C1 C2 was not changed compared with saline treated group. Successive 2 methyl 6 pyridine administration yielded a marked decrease in the number of pERK IR cells in the ipsilateral Vc and C1 C2 on day 8 after CFA injection into the tongue, whereas no change was found in the contralateral side. Continuous i. t. administration of MPEP for 7 days partially but significantly suppressed the decrement of both MHWT and HHWT on day 8 after CFA injection.

However, both MHWT and HHWT values were still lower in MPEP administrated CFA treated rats than the threshold value before CFA in jection on day 8, implicating an incomplete abolishment of CFA induced mechanical and thermal hypersensitivity by MPEP administration. Continuous i. t. administration Inhibitors,Modulators,Libraries of 2 Chloro 5 hydroxyphenylglycine for 7 days induced Inhibitors,Modulators,Libraries the Inhibitors,Modulators,Libraries decrement of MHWT on day 8 compared with saline administrated group in naive rats, implicating that mGluR5 activation in Vc and C1 C2 neurons is sufficient to induce mechanical allody nia in the tongue. Discussion Inflammatory tongue pain model In spite of previous extensive research efforts into the pathogenesis of extra oral pain, limited information is now available concerning pathological pain occurring in the tongue, which causes great difficulty in diagnosis and treatment of tongue related diseases in the clinic.

There fore, it is quite necessary to devise new preclinical mod els of pathological Inhibitors,Modulators,Libraries tongue pain in order to gain better understanding selleckchem Nutlin-3a of the underlying mechanisms and hence provide more effective therapeutic approaches. In this context, several models of orofacial neuropathic pain induced by lingual nerve injury have been previously developed and intensively characterized.