Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation

Li, Xuhui; Matsuura, Takanori; Xue, Mingshan; Chen, Qi-Yu; Liu, Renhao; Lu, Jing-Shan; Shi, Wantong; Fan, Kexin; Zhou, Zhaoxiang; Zhang, Miao; Yang, Jiale; Wei, Sara; Feng, Wei; Chen, Tao; Zhuo, Min

doi:10.1016/j.celrep.2021.109411

Cited by 117 publications

(72 citation statements)

References 51 publications

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“…In this study, the unaltered LTD suggested that LTD in ACC is not involved in chronic pain in PD mice. Presynaptic synaptic plasticity has been identified as playing an important role in chronic pain and anxiety [ 12 , 14 , 25 , 27 ]. Therefore, the presynaptic enhancement of neurotransmitter release in the ACC may contribute to the chronic pain and anxiety in mice of PD model.…”

Section: Discussionmentioning

confidence: 99%

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Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease

Zhou

et al. 2021

Mol Brain

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Parkinson’s disease (PD) is a multi-system neurodegenerative disorder. Patients with PD often suffer chronic pain. In the present study, we investigated motor, sensory and emotional changes in three different PD mice models. We found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treatment caused significant changes in all measurements. Mechanical hypersensitivity of PD model induced by MPTP peaked at 3 days and persisted for at least 14 days. Using Fos transgenic mice, we found that neurons in the anterior cingulate cortex (ACC) were activated after MPTP treatment. Inhibiting ACC by bilateral microinjection of muscimol significantly reduced mechanical hypersensitivity and anxiety-like responses. By contrast, MPTP induced motor deficit was not affected, indicating ACC activity is mostly responsible for sensory and emotional changes. We also investigated excitatory synaptic transmission and plasticity using brain slices of MPTP treated animals. While L-LTP was blocked or significantly reduced. E-LTP was not significantly affected in slices of MPTP treated animals. LTD induced by repetitive stimulation was not affected. Furthermore, we found that paired-pulse facilitation and spontaneous release of glutamate were also altered in MPTP treated animals, suggesting presynaptic enhancement of excitatory transmission in PD. Our results suggest that ACC synaptic transmission is enhanced in the animal model of PD, and cortical excitation may play important roles in PD related pain and anxiety.

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Section: Discussionmentioning

confidence: 99%

“…Spontaneous EPSCs (sEPSCs) were recorded with the K-gluconate internal solution and holding − 60 mV. Picrotoxin (100 µM) was always present to block GABA A receptor-mediated inhibitory synaptic currents in all experiments [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease

Zhou

et al. 2021

Mol Brain

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“…Most of these brain regions are consistent with the BOLD signals increased brain areas in our study. In addition, oxytocin (mainly produced in the PVN) in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety (Li et al, 2021), revealing that the PVN and Cg have structural or functional connections. Taking the PVN as the seed, it was found that the functional connectivity (FC) between the PVN and the olfactory nucleus, the Cg, the PVT, the PAG, the motor cortex, the caudateputamen, and hippocampus increased after CNO injection (Figure 1D; Table 1).…”

Section: Resultsmentioning

confidence: 99%

Distinct Hypothalamic Paraventricular Nucleus Inputs to the Cingulate Cortex and Paraventricular Thalamic Nucleus Modulate Anxiety and Arousal

Liu

Rao

et al. 2022

Front. Pharmacol.

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Insomnia and anxiety are two common clinical diseases that threaten people’s physical and mental health. Insomnia and anxiety may share some similar underlying neural circuit mechanisms in the brain. In this study, we combine techniques including chemo-fMRI, optogenetics, and chemogenetics to reveal that the glutamatergic neurons of the paraventricular hypothalamic nucleus (PVN) regulate both anxiety and arousal through two different downstream neural circuits. Optogenetic activation of the PVN-cingulate cortex (Cg) neural circuit triggers anxiety-like behaviors in mice without affecting the wakefulness, while optogenetic activation of the PVN-paraventricular thalamic nucleus (PVT) neural circuit promotes wakefulness in mice without affecting anxiety-like behaviors. Our research reveals that PVN is a key brain area for controlling anxiety and arousal behaviors. We also provide a neurological explanation for anxiety disorder and insomnia which may offer guidance for treatments including drugs or transcranial magnetic stimulation for the patients.

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“…Chronic social defeat stress has been reported to decrease expression of oxytocin receptor mRNA in the ACC, inducing anxiety-related behaviors. Oxytocin injection into the ACC has been shown to attenuate nociceptive responses and anxiety-related behavior in animals with neuropathic pain by selectively blocking the maintenance of presynaptic long-term potentiation (LTP) but not postsynaptic LTP [ 112 ]. In humans, intranasal oxytocin has been shown to reduce activation of the dorsal part of the ACC in response to fearful faces in men, while intranasal oxytocin increased ACC activation in women [ 113 ].…”

Section: Stress Responses and Oxytocinmentioning

confidence: 99%

Roles of Oxytocin in Stress Responses, Allostasis and Resilience

Takayanagi

Onaka

2021

IJMS

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Oxytocin has been revealed to work for anxiety suppression and anti-stress as well as for psychosocial behavior and reproductive functions. Oxytocin neurons are activated by various stressful stimuli. The oxytocin receptor is widely distributed within the brain, and oxytocin that is released or diffused affects behavioral and neuroendocrine stress responses. On the other hand, there has been an increasing number of reports on the role of oxytocin in allostasis and resilience. It has been shown that oxytocin maintains homeostasis, shifts the set point for adaptation to a changing environment (allostasis) and contributes to recovery from the shifted set point by inducing active coping responses to stressful stimuli (resilience). Recent studies have suggested that oxytocin is also involved in stress-related disorders, and it has been shown in clinical trials that oxytocin provides therapeutic benefits for patients diagnosed with stress-related disorders. This review includes the latest information on the role of oxytocin in stress responses and adaptation.

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Oxytocin in the anterior cingulate cortex attenuates neuropathic pain and emotional anxiety by inhibiting presynaptic long-term potentiation

Cited by 117 publications

References 51 publications

Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease

Synaptic potentiation of anterior cingulate cortex contributes to chronic pain of Parkinson’s disease

Distinct Hypothalamic Paraventricular Nucleus Inputs to the Cingulate Cortex and Paraventricular Thalamic Nucleus Modulate Anxiety and Arousal

Roles of Oxytocin in Stress Responses, Allostasis and Resilience

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