RT Journal Article
SR Electronic
T1 Trigeminal nerve transection-induced neuroplastic changes in the somatosensory and insular cortices in a rat ectopic pain model
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0462-18.2019
DO 10.1523/ENEURO.0462-18.2019
A1 Satoshi Fujita
A1 Kiyofumi Yamamoto
A1 Masayuki Kobayashi
YR 2019
UL http://www.eneuro.org/content/early/2019/01/10/ENEURO.0462-18.2019.abstract
AB The primary sensory cortex processes competitive sensory inputs. Ablation of these competitive inputs induces neuroplastic changes in local cortical circuits. However, information concerning cortical plasticity induced by a disturbance of competitive nociceptive inputs is limited. Nociceptive information from the maxillary and mandibular molar pulps converges at the border between the ventral secondary somatosensory cortex (S2) and insular oral region (IOR), therefore S2/IOR is a suitable target for examining the cortical changes induced by a disturbance of noxious inputs, which often causes neuropathic pain and allodynia. We focused on the plastic changes in S2/IOR excitation in a model of rats subjected to inferior alveolar nerve transection (IANX). Our optical imaging using a voltage-sensitive dye revealed that the maxillary molar pulp stimulation-induced excitatory propagation was expanded 1-2 weeks after IANX at the macroscopic level. At the cellular level, based on Ca2+ imaging using two-photon microscopy, the amplitude of the Ca2+ responses and the number of responding neurons in S2/IOR increased in both excitatory and inhibitory neurons. The in vitro laser scanning photostimulation revealed that layer II/III pyramidal and GABAergic fast-spiking neurons in S2/IOR received larger excitatory inputs from layer IV in the IANX models, which supports the findings obtained by the macroscopic and microscopic optical imaging. Furthermore, the inhibitory postsynaptic inputs to the pyramidal neurons were decreased in the IANX models, suggesting suppression of inhibitory synaptic transmission onto excitatory neurons. These results suggest that IANX induces plastic changes in S2/IOR by changing the local excitatory and inhibitory circuits. (246/250 words)Significance statement The inferior alveolar nerve (IAN), a mandibular branch of the trigeminal nerve, innervates the orofacial region, including the tooth pulps. IAN transection (IANX) induces allodynia in the maxillary nerve-projecting region. This study demonstrates the facilitation of excitatory propagation in the secondary somatosensory cortex (S2) and insular oral region (IOR) following maxillary molar tooth pulp stimulation in IANX rats. Both pyramidal and fast-spiking neurons in layer II/III S2/IOR of IANX rats received larger glutamatergic excitatory inputs from the deeper layers. Reduction of GABAA receptor-mediated IPSCs in pyramidal neurons of IANX rats may contribute to the facilitated excitation in S2/IOR. These findings suggest that GABAergic neurons in S2/IOR could be a therapeutic target for ectopic pain in the orofacial region. (118/120 words)