Mechanism of GABA involvement in post‐traumatic trigeminal neuropathic pain: Activation of neuronal circuitry composed of PKCγ interneurons and pERK1/2 expressing neurons

Abstract

The circuitry composed of PKCγ and pERK1/2 cells is silent under physiological conditions but is activated after CCI-IoN, therefore, switching touch stimuli to pain sensation. The decrease of GABA transmission constituted a key factor in the activation of this neuronal circuitry, which opens the gate for non-noxious stimuli to reach nociceptive projection neurons in lamina I.

Nigrostriatal dopaminergic depletion increases static orofacial allodynia

“…PKCγ is known to be a key molecule for the onset of pain chronicity [ 21 ]. Its expression increases after CCI-IoN confirming previous studies [ 22 , 24 , 28 ]. Our result suggests that the lesion of the dopaminergic nigrostriatal system increased the SMA by acting on PKCγ cells through descending pain inhibitory system.…”

“…Our result suggests that the lesion of the dopaminergic nigrostriatal system increased the SMA by acting on PKCγ cells through descending pain inhibitory system. PKCγ cells are known to activate a secondary cell subtype within MDH superficial laminae which expressed pERK1/2 [ 28 ] and the specific PKCγ inhibition decreased both the number of pERK1/2 cells and the related neuropathic pain behavior [ 24 ]. This highlights the essential role of PKCγ cells in inducing allodynia.…”

Nigrostriatal dopaminergic depletion produces orofacial static mechanical allodynia

“…B). This marker has been shown to be expressed by neurons (Shimizu et al., ; Hasegawa et al., ; Dieb and Hafidi, ). In 6‐OHDA‐lesioned rats most of the pERK1/2‐positive cells were observed in the superficial laminae I and IIi particularly in the side ipsilateral to the stimulus (Fig.…”

“…Since this is the first study which explored a static mechanical allodynia after 6‐OHDA administration, we compared its time‐course development to that obtained after CCI‐IoN within the orofacial region (Dieb and Hafidi, , ). 6‐OHDA‐lesioned rats were assessed for cSMA from 4 days to 12 weeks after injury (Fig.…”

“…Two markers were used to reveal segmental sensitization: (1) PKCγ, which labels cells within the MDH lamina II and plays a key role in the chronicity of pain (Malmberg et al., ); and (2) the phosphorylation of ERK 1/2 which occurred under noxious stimuli in the dorsal spinal cord (Ji et al., ). The later constitutes a molecular marker for pain processes and is expressed in neurons within the medullary dorsal horn after CCI‐IoN (Shimizu et al., ; Hasegawa et al., ; Dieb and Hafidi, ).…”