Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial XXXX after Nerve Injury via @entity2509 Activation in Insular Cortex Neurons.

@entity308 @entity550 @entity5732 @entity146 @entity1337 @entity2509 @entity5019 @entity158 @entity35 @entity9 @entity130
Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic @entity158 . However, the relationship between critical cortex excitability and @entity158 maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending @entity158 modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in @entity35 . Infraorbital nerve chronic @entity130 (IoN-CCI) induced significant @entity146 as well as @entity158 such as @entity308 in @entity35 . By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the @entity550 ( @entity550 ). @entity2509 ( @entity2509 ), an important signaling molecule involved in neuroplasticity, was significantly activated in the @entity550 following IoN-CCI. Moreover, in @entity550 slices from IoN-CCI @entity35 , @entity5732 , an inhibitor of @entity2509 activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, @entity5732 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra- @entity550 infusion of @entity5732 obviously decreased @entity5019 expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the @entity550 to the Vc could directly regulate @entity158 , and @entity2509 deactivation in the @entity550 could effectively alleviate @entity9 as well as @entity158 in IoN-CCI @entity35 , probably through this top-down pathway. These findings may help researchers and clinicians to better understand the underlying modulation mechanisms of orofacial @entity9 and indicate a novel mechanism of @entity2509 inhibitor-induced @entity1337 .
