administration of the MEK1 2 inhibitor PD98059 ef fectively attenuated the mechanical and heat hyper sensitivity in CFA injected rats, accompanied with an apparent decrease in the number of pERK IR neurons in the ipsilateral Vc. These observations suggest that the ERK pathway is involved in the enhancement of the excitability of Vc and selleck compound C1 C2 neurons following CFA injection into the tongue, resulting in the initi ation and or maintenance of mechanical and heat hypersensitivity in the inflamed tongue. Involvement of mGluR5 in ERK mediated inflammatory tongue pain The group I mGluRs are thought to play vital roles in mediation or modulation of nociceptive transmission at different levels of the central nerve system. mGluR5 mRNA and its protein are shown to be distributed in the spinal trigeminal nu cleus.

mGluR5 contributes to the induction of long term potentiation of primary afferent Inhibitors,Modulators,Libraries synaptic transmission in the superficial layer of the Vc, and modulates inflammatory nociceptive plasticity via down stream activation of ERK signaling in the spinal cord. The amount of glutamate which is an endogen ous ligand of mGluR5 increases in the dorsal horn fol lowing peripheral injection of inflammatory agents. All of these previous findings make it very likely that mGluR5 serves as an upstream activator for CFA induced ERK phosphorylation. Supporting this hypoth esis, we documented that mGluR5 was colocalized with pERK in Vc and C1 C2 neurons. Moreover, continuous i. t. administration of the selective mGluR5 antagonist MPEP significantly Inhibitors,Modulators,Libraries blocked CFA evoked mechanical and heat hypersensitivity in the inflamed tongue and reduced the number of pERK IR cells in ipsilateral Vc and C1 C2.

On the other hand, direct mGluR5 activation by i. t. CHPG administration induced mechanical allodynia in the tongue in naive rats. The present findings suggest that the mGluR5 activation in Vc and C1 C2 neurons by CFA evoked glutamate Inhibitors,Modulators,Libraries release in the dorsal horn med iates ERK phosphorylation, and then Vc and C1 C2 neuronal excitability is enhanced, leading to mechanical and heat hypersensitivity in the rats with CFA injection into the tongue. However, pre treatment with i. t. administration of MPEP failed to completely abolish the upregulation of pERK IR cells and the reduction of MHWT and HHWT on day 8 after CFA injection into the tongue, indicating that there are other upstream activators for neuronal hyperexcitability in Vc and C1 C2.

For instance, ionotro pic glutamate receptors and Inhibitors,Modulators,Libraries some other protein kinases play an important role in ERK mediated enhancement of neuronal excitability in the dorsal horn. In addition, inflammation evoked ERK activation, which is required for nociceptive plasticity, Inhibitors,Modulators,Libraries selleck chemicals llc is also the down stream of mGluR1. Antisense oligonucleotide knockdown of spinal mGluR1 attenuates heat hyperalge sia and mechanical allodynia in rats with CFA injection into the hindpaw.