Glycogen in spinal astrocytes intensifies pain perception.
A recent study published in Nature Metabolism sheds light on a mechanism for pain sensitization involving a regulatory protein of glycogen metabolism in spinal astrocytes. Chronic pain poses a significant challenge to society due to its impact on well-being, increasing prevalence, and associated healthcare costs. The study explores the cellular level mechanisms underlying chronic pain, highlighting the interactions between astrocytes and neurons in the spinal cord as potential contributors to pain sensitization.
Astrocytes in the central nervous system play a crucial role in regulating synaptic function through their metabolic activities, characterized by elevated levels of NADH/NAD+ ratios and lactate compared to neurons. The study unveils the involvement of glycogen deposits in spinal astrocytes in regulating pain sensitization, a role previously unknown. The research conducted by Marty-Lombardi et al. utilized advanced techniques like ribosome isolation combined with RNA sequencing to identify the active transcripts in spinal cord samples from mice subjected to noxious stimuli. The findings revealed that the gene Ptg (protein targeting to glycogen) was upregulated in spinal astrocytes in response to pain stimuli, suggesting a link between glycogen metabolism and pain sensitivity.
Further investigations demonstrated complex glycogen dynamics in the spinal cord, with glycogen levels fluctuating in response to prolonged noxious stimuli. The study showed that the accumulation of glycogen in spinal astrocytes, regulated by PTG expression, was crucial for pain sensitization. Knockout experiments confirmed the pivotal role of PTG in glycogen accumulation and pain hypersensitivity. Manipulating PTG levels in astrocytes influenced pain sensitivity, indicating the potential for targeting this pathway for pain management.
The study also delved into the metabolic consequences of glycogen accumulation, showcasing the breakdown of accumulated glycogen and its impact on lactate production. The authors observed a higher glycolytic rate in response to neuronal activation in tissues with accumulated glycogen. Moreover, the study highlighted the role of lactate in modulating neuronal activity and the establishment of a hyperexcitable phenotype in the spinal cord. The findings suggested that astrocytic glycogenolysis and lactate production influenced neuronal function and pain sensitization.
The research opens up new avenues for understanding the intricate interplay between astrocytes and neurons in the context of pain regulation. It underscores the importance of metabolic cooperation between these cell types in modulating pain sensitivity. The study's implications extend to potential therapeutic interventions for chronic pain by targeting glycogen metabolism in spinal astrocytes. Overall, the study provides valuable insights into the mechanisms underlying pain sensitization and offers promising prospects for developing novel pain management strategies.
Source: https://www.nature.com/articles/s42255-024-01000-3
Astrocytes in the central nervous system play a crucial role in regulating synaptic function through their metabolic activities, characterized by elevated levels of NADH/NAD+ ratios and lactate compared to neurons. The study unveils the involvement of glycogen deposits in spinal astrocytes in regulating pain sensitization, a role previously unknown. The research conducted by Marty-Lombardi et al. utilized advanced techniques like ribosome isolation combined with RNA sequencing to identify the active transcripts in spinal cord samples from mice subjected to noxious stimuli. The findings revealed that the gene Ptg (protein targeting to glycogen) was upregulated in spinal astrocytes in response to pain stimuli, suggesting a link between glycogen metabolism and pain sensitivity.
Further investigations demonstrated complex glycogen dynamics in the spinal cord, with glycogen levels fluctuating in response to prolonged noxious stimuli. The study showed that the accumulation of glycogen in spinal astrocytes, regulated by PTG expression, was crucial for pain sensitization. Knockout experiments confirmed the pivotal role of PTG in glycogen accumulation and pain hypersensitivity. Manipulating PTG levels in astrocytes influenced pain sensitivity, indicating the potential for targeting this pathway for pain management.
The study also delved into the metabolic consequences of glycogen accumulation, showcasing the breakdown of accumulated glycogen and its impact on lactate production. The authors observed a higher glycolytic rate in response to neuronal activation in tissues with accumulated glycogen. Moreover, the study highlighted the role of lactate in modulating neuronal activity and the establishment of a hyperexcitable phenotype in the spinal cord. The findings suggested that astrocytic glycogenolysis and lactate production influenced neuronal function and pain sensitization.
The research opens up new avenues for understanding the intricate interplay between astrocytes and neurons in the context of pain regulation. It underscores the importance of metabolic cooperation between these cell types in modulating pain sensitivity. The study's implications extend to potential therapeutic interventions for chronic pain by targeting glycogen metabolism in spinal astrocytes. Overall, the study provides valuable insights into the mechanisms underlying pain sensitization and offers promising prospects for developing novel pain management strategies.
Source: https://www.nature.com/articles/s42255-024-01000-3
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