Host: The Japanese Pharmacological Society
Name : The 95th Annual Meeting of the Japanese Pharmacological Society
Number : 95
Location : Fukuoka
Date : March 07, 2022 - March 09, 2022
Orofacial neuropathic pain dampens QOL by disturbing daily activates including chewing and talking. Accumulating evidence indicates the importance of cytokines, such as interleukin (IL)-1 beta and IL-18, in the development of neuropathic pain; however, the role of IL-33, a member of IL-1 family, in neuropathic pain has not been fully understood. Here, we investigate the role of IL-33 in orofacial neuropathic pain using infraorbital nerve injury (IONI) mice. Mechanical allodynia in the whisker pad skin and an increase in the amount of IL-33 in the Vc were observed following IONI. IL-33 and its receptor were exclusively expressed in oligodendrocytes and neurons, respectively. IONI-induced mechanical allodynia was ameliorated by neutralizing IL-33 in the Vc. Conversely, intracisternal administration of IL-33 triggered mechanical allodynia in naïve mice without affecting glial activation. Intracisternal administration of IL-33 facilitated phosphorylation of GluN2B, a subunit of NMDA receptor, in the synaptosomal fraction from the Vc and potentiated GluN2B-mediated miniature excitatory postsynaptic currents in the Vc. Furthermore, a specific GluN2B antagonist reversed IL-33-induced mechanical allodynia. Intracisternal administration of IL-33 caused phosphorylation of Fyn kinase but not Src kinase. Following IL-33 administration, phosphorylated Fyn kinase was located in the dendritic spine of the Vc. Inhibition of Fyn phosphorylation decreased IL-33-induced phosphorylated GluN2B in the Vc and prevented IL-33-induced mechanical allodynia. These results suggest that oligodendrocytes-derived IL-33 activates Vc neurons by phosphorylation of Fyn kinase and subsequent phosphorylation of GluN2B, culminating in the orofacial neuropathic pain. Our results lead to the development of orofacial neuropathic pain targeting the IL-33 signaling.
