Science Sub-Journal: Neural Circuit Mechanisms of Chronic Pain-Induced Anxiety

Click on the blue word to focus on our pain perception as a physiological warning of impending or actual tissue damage
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But long-term chronic pain is a pathological state that can cause anxiety, depression and other adverse affective disorders
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The bed nucleus of stria terminalis (BNST) is an important brain region for encoding negative emotions such as anxiety and fear.
Selective activation of the anterior dorsal part of BNST (adBNST) projects to the lateral hypothalamus (LH) to produce anxiolytic effects
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April 27, 2022 Masabumi Minami's research team at Hokkaido University, Japan, found that mice with pain induced by nerve fiber damage exhibited marked anxiety-like behaviors, and further revealed that the local inhibitory circuit of BNST mediates this pain-anxiety comorbidity disorder
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Neurons projecting from adBNST to the LH region can be divided into corticotropin-releasing factor and cholecystokinin subgroups according to their secreted peptides, where the former encodes reward information and the latter encodes aversive stimuli
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Here we divide the neuronal electrical activity into positive and negative hyperpolarization-activated cation currents
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Electrophysiological experiments showed that most (about 80%) neurons projecting from adBNST to the LH region exhibited negative hyperpolarization-activated cation currents, and chronic pain further enhanced the spontaneous inhibitory postsynaptic currents projected by adBNST to LH neurons.
increased, suggesting that chronic pain enhances inhibitory input of adBNST projections to the LH
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Chemogenetic-specific inhibition of the adBNST → LH circuit induces anxiety-like behaviors
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Activation of this neural circuit can significantly alleviate anxiety-like behaviors caused by chronic pain
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Similar to the amygdala, complex local inhibitory circuits also exist in the BNST region
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The researchers found that adBNST receives input from the oval region of BNST (ovBNST).
Since more than 80% of neurons in this region express cocaine-amphetamine-regulated transcription peptide (CART), CARTergic neurons in the ovBNST brain region may serve as adBNST → Inhibitory input to the LH loop
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To confirm this problem, they injected inhibitory optogenetic virus into the ovBNST brain region of CART-cre mice, and injected retrograde tracer virus into the LH.
After photoinhibition of ovBNST, they were able to induce spontaneous inhibitory processes of adBNST → LH projection neurons.
Aftertouch currents, indicating that there are inhibitory inputs to the adBNST → LH loop from CARTergic neurons in the ovBNST brain region
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Further electrophysiological experiments found that chronic pain caused by nerve fiber damage can enhance the excitability of CARTergic neurons in the ovBNST brain region
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Chemogenetic inhibition of CARTergic neuron activity in the ovBNST brain region can attenuate chronic pain-induced anxiety-like behaviors and partially block the inhibitory current enhancement effect of chronic pain-induced adBNST → LH loop
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This suggests that the enhanced excitability of CARTergic neurons in the ovBNST brain region is the key electrical activity in chronic pain-induced anxiety-like behaviors
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Overall, we found that chronic pain can enhance the excitability of CARTergic neurons in the ovBNST brain region of the BNST subregion, and induce anxiety-like behaviors through a local inhibitory loop regulating the adBNST → LH loop
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【References】1.
Chronic pain–induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety The pictures in the text are from references