Abstract
Although astrocytes are known to regulate synaptic transmission and affect new memory formation by influencing long-term potentiation and functional synaptic plasticity, their role in pain modulation is poorly understood. Motor cortex stimulation (MCS) has been used to reduce neuropathic pain through the incertothalamic pathway, including the primary motor cortex (M1) and the zona incerta (ZI). However, there has been no in-depth study of these modulatory effects and region-specific changes in neural plasticity. In this study, we investigated the effects of MCS-induced pain modulation as well as the relationship between the ZI neuroplasticity and MCS-induced pain alleviation in neuropathic pain (NP). MCS-induced threshold changes were evaluated after daily MCS. Then, the morphological changes of glial cells were compared by tissue staining. In order to quantify the neuroplasticity, MAP2, PSD95, and synapsin in the ZI and M1 were measured and analyzed with western blot. In behavioral test, repetitive MCS reduced NP in nerve-injured rats. We also observed recovered GFAP expression in the NP with MCS rats. In the NP with sham MCS rats, increased CD68 level was observed. In the NP with MCS group, increased mGluR1 expression was observed. Analysis of synaptogenesis-related molecules in the M1 and ZI revealed that synaptic changes occured in the M1, and increased astrocytes in the ZI were more closely associated with pain alleviation after MCS. Our findings suggest that MCS may modulate the astrocyte activities in the ZI and synaptic changes in the M1. Our results may provide new insight into the important and numerous roles of astrocytes in the formation and function.
Highlights
Astrocytes are known to regulate synaptic transmission and affect new memory formation by influencing long-term potentiation and functional synaptic plasticity, their role in pain modulation is poorly understood
We focused on the relationship between pain modulation after Motor cortex stimulation (MCS) and neuronal plastic changes in the zona incerta (ZI), which has been associated with astrocyte-induced synapse modulation
We evaluated the changes in chronic neuropathic pain (NP)-induced neural plasticity following MCS by assessing behavior, morphology, and local synaptic protein expression
Summary
Astrocytes are known to regulate synaptic transmission and affect new memory formation by influencing long-term potentiation and functional synaptic plasticity, their role in pain modulation is poorly understood. Chronic neuropathic pain (NP) is the result of primary lesion in peripheral nerve and/or central nervous system (CNS) dysfunction in the absence of nociceptor stimulation[1] This multidimensional clinical entity is mediated by various pathophysiological mechanisms, making its treatment difficult[2,3]. Increased spontaneous and evoked activity in the ZI is causally related to repetitive MCS10 These findings strongly implicate the ZI as a site of maladaptive plasticity in chronic pain modulation. Using a rat model of chronic NP, we compared neuronal changes after MCS and measured various markers of astrocyte plasticity in the ZI. Our findings suggest that MCS may modulate astrocyte activities in the ZI and synaptic changes in the M1 These results clarify the mechanism of MCS-induced analgesic effects in the setting of chronic NP
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