Regulation of nociception by long-term potentiation of inhibitory postsynaptic currents from insular cortical parvalbumin-immunopositive neurons to pyramidal neurons.
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引用次数: 0
Abstract
Abstract: The insular cortex (IC) processes various sensory information, including nociception, from the trigeminal region. Repetitive nociceptive inputs from the orofacial area induce plastic changes in the IC. Parvalbumin-immunopositive neurons (PVNs) project to excitatory neurons (pyramidal neurons [PNs]), whose inputs strongly suppress the activities of PNs. This study investigated how PVNs in the IC modulate pain-related behaviors using optogenetics. To evaluate the effect of PVN activation on pain-related behavior, we applied nociceptive heat stimulation to the whisker pads of PV-Cre rats that received an injection of adeno-associated virus-Flex-channelrhodopsin-2-mCherry into the IC. Exposure to nociceptive heat stimulation significantly increased the amount of pain-related escape behavior, and PVN activation by optogenetics did not significantly decrease pain-related behavior. We next examined the possibility that long-term potentiation (LTP) of PVN→PN synapses suppresses pain-related behaviors. We recorded light-evoked inhibitory postsynaptic currents (IPSCs) from PNs in the IC slice preparation to examine whether optogenetic activation of PVNs can induce LTP. Repetitive optogenetic stimulation (ROS) of PVNs in a manner analogous to theta burst stimulation increased the amplitude of IPSCs for at least 50 minutes. Long-term potentiation was induced by either the -45 or -60 mV membrane potential of PNs. Then, the IC received ROS to induce LTP of IPSCs from PVNs to PNs, and we evaluated pain-related behaviors. Compared to those before ROS, the pain-related behaviors were further reduced after ROS. These results suggest that LTP induction of PVN→PN synapses in the IC could be a possible treatment for abnormal pain in the orofacial area.
期刊介绍:
PAIN® is the official publication of the International Association for the Study of Pain and publishes original research on the nature,mechanisms and treatment of pain.PAIN® provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest.