Synaptic association and functional space and temporal plasticity of hippocampal formation associated with persistent pain: planar microelectrode array recording technique

Persistent contact and functional space and temporal plasticity in hippocampal formation associated with persistent pain:

Planar microelectrode array recording technology

Zhao Xiaoyan Yuan Dongliang ^{2 1 1} Max Liu He Ying Wang Yan ^{2 1 2} Zhangfu Kang Chen Xuefeng Dandan ^{1 1 1} Hexiao Sheng Hua Chen Jun ^{2 1,2 *} (* Corresponding author)

¹ Institute of Pain Biomedicine, Capital Medical University, Beijing 100069, China

² Institute of Pain Biomedicine, Fourth Military Medical University, Xi'an 710038, China

Summary

Background: It is well known that pain is mediated by a complex neural network (neural matrix) present in the brain. In the state of pathological pain, persistent or chronic pain affects many advanced brain functions, which in turn causes symptoms associated with pain such as anxiety, insomnia, motor dysfunction, forgetting, depression, and disability. Unfortunately, what is the impact of pathological pain on advanced brain function? What is the structure and function of the brain neural network in pain? So far, there have been few such studies, which have greatly hindered the treatment of pain and complications. In this study, we applied planar microelectrode array recording technology for the first time. At the neural network level, continuous pain stimulation was observed to cause synaptic connections in hippocampal formation and plasticity changes in both functional time and space.

Experimental results: Adult rats who had experienced two hours of persistent pain in advance were anesthetized and decapitated to prepare hippocampal slices. The persistent pain model used was two persistent pain models of the bee venom test and the formalin test. The 64-plane microelectrodes developed by Panasonic Alpha-Med Science in Japan were recorded in a multi-point synchronous recording by a data acquisition and recording system (MED64 system) arranged in an 8×8 array. It is known that the hippocampal dentate gyrus and the CA1 region can accept direct afferent fibers from the anterior cortex and form a direct synaptic connection. Two types of field potentials can be recorded in the hippocampal formation by a single electrical stimulation on the cortical fiber bundle pathway in front of the hippocampus. The dentate gyrus is a forward wave with a peak upward, while in the CA1 region, The negative wave below the peak is normally a single-phase wave. Pharmacologically, both types of field potentials are excitatory amino acid (glutamate) ion-gated receptor-mediated excitatory postsynaptic field potentials. In this experiment, we observed that continuous painful experiences can cause plasticity changes in both spatial and temporal aspects of hippocampal structural neural networks. In terms of spatial synaptic plasticity, peripheral persistent pain can cause increased synaptic connections in the dentate gyrus and CA1, such as a significant increase in the number of effective excitatory postsynaptic potentials recorded at 65 recording electrodes, suggesting persistent pain states. The lower hippocampus structure formed a new synaptic connection through space recruitment, and this result was not recorded with a single electrode. At the cellular level, by comparing the intensity-synaptic field potential amplitude curve analysis of each node of the neural network, it was found that the rats with persistent pain experienced a functional curve compared with the rats without persistent pain (if no treatment group and The apparent left shift of the peripheral saline injection physiological pain group indicated that the synaptic transmission efficiency of the neural network was significantly enhanced synchronously under the same stimulation parameters. In terms of temporal synaptic plasticity, generally under normal circumstances, a θ rhythm conditional stimulus associated with acetylcholine release induces a long-term potentiation effect of synaptic transmission in the dentate gyrus and CA1 region, which is called LTP (long -term potentiation). We found that when there was persistent painful stimulation in the periphery, the LTP induction rate was increased by 10% (from 60%-70% to over 80%) in the same parameter than in the non-sustained pain-stimulated group, and the intensity of LTP was also increased. 100% (from 160%-170% to more than 260%). More interestingly, under the condition of persistent pain, θ rhythm stimulation can be used to observe the shape of the excitatory postsynaptic field potential from a smooth single-phase wave to a deformed complex phase wave on about 50% of hippocampal slices. The level of local synaptic loops in the hippocampal formation is reconstructed. In order to answer whether the spatial and temporal neural network synaptic plasticity changes in hippocampal formation are related to peripheral persistent pain, we infiltrated the local anesthetic bupivacaine in the peripheral plantar of rats, and then injected pain-killing chemicals into the site. The display of blocking peripheral pain information can completely eliminate the above-mentioned synaptic plasticity and clarify the effect of pain on the hippocampus.

CONCLUSIONS: Peripheral persistent or chronic pain experiences can have a dramatic impact on high-level brain structures, leading to changes in synaptic connections and functions in the hippocampal structural neural network, such as spatially increasing synaptic connections and enhancing synaptic efficacy over time. The spatial plasticity change caused by pain is more complicated than the time plasticity, which is mainly reflected in the expansion of synaptic connection at the level of neural network and the reconstruction of local synaptic loop.