Functional disruption of cortical cingulate activity attenuates visceral hypersensitivity and anxiety induced by acute experimental colitis

Abstract

Visceral pain is a highly complex experience and is the most common pathological feature in patients suffering from inflammatory gastrointestinal disorders. Whilst it is increasingly recognized that aberrant neural processing within the gut-brain axis plays a key role in development of neurological symptoms, the underlying mechanisms remain largely unknown. Here, we investigated the cortical activation patterns and effects of non-invasive chemogenetic suppression of cortical activity on visceral hypersensitivity and anxiety-related phenotypes in a well-characterized mouse model of acute colitis induced by dextran sulfate sodium (DSS). We found that within the widespread cortical network, the mid-cingulate cortex (MCC) was consistently highly activated in response to innocuous and noxious mechanical stimulation of the colon. Furthermore, during acute experimental colitis, impairing the activity of the MCC successfully alleviated visceral hypersensitivity, anxiety-like behaviors and visceromotor responses to colorectal distensions (CRDs) via downregulating the excitability of the posterior insula (PI), somatosensory and the rostral anterior cingulate cortices (rACC), but not the prefrontal or anterior insula cortices. These results provide a mechanistic insight into the central cortical circuits underlying painful visceral manifestations and implicate MCC plasticity as a putative target in cingulate-mediated therapies for bowel disorders.

Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study

“…Researchers showed that regional characteristics of neuronal activity in the PoCG was linked to depression severity (Tadayonnejad et al, 2015). In first-episode MDD patients, researchers discovered greater local efficiency of the right PCL when compared to HCs (Chen et al, 2022). Furthermore, stronger PCL-amygdala resting-state FC has been reported in mood disorders with suicidal behavior (Zhang R. et al, 2020).…”

“…In addition, the right MCC decreased ReHo after taVNS was significantly positively correlated with the decreased of HAMD scores. The MCC has been linked to cognitive regulation, negative affect processing, and pain processing ( Wong et al, 2019 ; Brenner et al, 2021 ). Decreased functional connectivity (FC) between the MCC and other brain areas was attributed to decreased depression after antidepressant medication ( Tan et al, 2020 ).…”

Visceral pressure stimulator for exploring hollow organ pain: a pilot study

“…While there are no commercial comparisons to the VPS, there are reports in the literature of other custom units [13][14][15] or methods of pressure reading and recording [16,17]. To our knowledge, none of these other units are described in detail preventing a clear comparison of advantages and disadvantages to the VPS.…”

Tandem Mass Tag Analysis of the Effect of the Anterior Cingulate Cortex in Nonerosive Reflux Disease Rats with Shugan Jiangni Hewei Granules Treatment

“…Interestingly, the effect is mutual; several studies have found that irritability, anxiety, and other psychological effects of long-term stimulation can make the central nervous system (CNS)—including the anterior cingulate gyrus, amygdala, insula, hypothalamus, prefrontal cortex, and other brain areas—show abnormal activation, thereby aggravating the degree of VH [ 12 , 13 ]. Mechanical stimulation of the colon results in persistent hyperactivation of the middle cingulate cortex; in acute colitis, downregulation of anterior cingulate cortex excitability successfully attenuates visceral hypersensitivity, anxiety-like behaviors, and visceral motor response [ 14 ]. CNS neurons in a VH state demonstrated increased release of a variety of neurotransmitters, which are mostly encapsulated in vesicles for transport [ 15 ].…”