Anterior insular cortex mediates hyperalgesia induced by chronic pancreatitis in rats

Abstract

Central sensitization plays a pivotal role in the maintenance of chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. This study was designed to examine the role of anterior insular cortex (aIC) in the pathogenesis of hyperalgesia in a rat model of CP. CP was induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). Abdomen hyperalgesia and anxiety were assessed by von Frey filament and open field tests, respectively. Two weeks after surgery, the activation of aIC was indicated by FOS immunohistochemical staining and electrophysiological recordings. Expressions of VGluT1, NMDAR subunit NR2B and AMPAR subunit GluR1 were analyzed by immunoblottings. The regulatory roles of aIC in hyperalgesia and pain-related anxiety were detected via pharmacological approach and chemogenetics in CP rats. Our results showed that TNBS treatment resulted in long-term hyperalgesia and anxiety-like behavior in rats. CP rats exhibited increased FOS expression and potentiated excitatory synaptic transmission within aIC. CP rats also showed up-regulated expression of VGluT1, and increased membrane trafficking and phosphorylation of NR2B and GluR1 within aIC. Blocking excitatory synaptic transmission significantly attenuated abdomen mechanical hyperalgesia. Specifically inhibiting the excitability of insular pyramidal cells reduced both abdomen hyperalgesia and pain-related anxiety. In conclusion, our findings emphasize a key role for aIC in hyperalgesia and anxiety of painful CP, providing a novel insight into cortical modulation of painful CP and shedding light on aIC as a potential target for neuromodulation interventions in the treatment of CP.

Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

“…Unfortunately, much less focus has been directed toward the relief of the affective dimension of pancreatitis-related pain in both clinical and preclinical studies. In this study, we found that CP rats exhibited hypolocomotion and decreased exploratory behavior both in the open field and elevated plus maze tests, consistent with prior behavioral observations in VH rats induced by irritable bowel syndrome and chronic pancreatitis [31,34].…”

“…Sham rats exhibited a transient decrease of AWT, which reached a minimum on POD 3 and returned to baseline on POD 14. This phenomenon was also seen in our previous study, and was owing to post-operative pain [34]. Compared to sham rats, CP rats had a lower AWT from POD 7 to 35 (Fig.…”

Targeting neuroinflammation with Abscisic Acid reduces pain sensitivity in females and hyperactivity in males of an ADHD mice model

“…One of which, the anterior cingulate cortex (ACC) that receives sensitive information via the thalamus and projects to the insular cortex (IC) has been well-characterized [37,38]. ACC hyperexcitability is associated to higher levels of pain [39], and glia activation can trigger hyperexcitability modulating neuronal channel function [40]. Furthermore, inflammatory markers in ACC are linked to pain sensitization [41–43], thus we aimed to test whether dopaminergic dysfunction underlying ADHD symptoms could cause ACC inflammation, so, consequently reducing inflammation would alleviate ADHD symptomatology.…”

Anterior Insular-nucleus Accumbens Pathway Controls Refeeding-induced Analgesia under Chronic Inflammatory Pain Condition

“…The anterior insular cortex (aIC) is also highly implicated in feeding behavior and pain perception [18][19][20], and tracing studies in rodents have shown that the NAc receives glutamatergic input from the aIC [21].…”