Brain mechanisms underlying chronic visceral pain and its association with affective behaviors in the absence of measurable pathology

Authors

• S Martinez Gonzalez
• C Pichardo
• Y Carrasquillo

Abstract

Chronic visceral pain is often characterized by visceral hypersensitivity in the absence of measurable pathology. While it has been reported that visceral hypersensitivity correlates with the development of maladaptive changes in affective behaviors, the brain mechanisms underlying the comorbidity of chronic visceral pain and changes in affective behaviors in the absence of identifiable pathology is not clearly defined. The main goal of the present study is to begin to address these questions using rodent models of chronic visceral pain. Rodent behavioral assays that recapitulate the association between chronic visceral pain and comorbid affective behaviors in the absence of measurable pathology, however, have not been previously described. For this reason, the first goal of the present study is to establish a rodent behavioral assay that recapitulates this association. The Dextran Sodium Sulfate rodent model of visceral pain was selected because it has been previously shown to induce visceral hypersensitivity that persists following the full recovery of visceral pathology. The elevated zero maze and open field test will be used to measure anxiety-like behaviors and the forced swim test to measure depression-like behaviors at time-points where visceral hypersensitivity is present but visceral pathology has fully recovered. Given that chronic visceral pain is more prevalent in female patients, parallel experiments in this study were aimed at evaluating baseline abdominal sensitivity in male and female subjects at different stages of the estrous cycle, with the long-term goal of performing our mechanistic studies in both male and female subjects. Consistent with clinical studies, our preliminary results in rodents demonstrate that abdominal sensitivity is similar in male and female subjects in the estrous, metestrous and diestrous stages but is significantly lower in females in the proestrous stage, compared to males and females in estrous, metestrous and diestrous. Future experiments will evaluate the contribution of distinct cell types in the brain to the modulation comorbid chronic visceral pain and maladaptive changes in affective behaviors in the absence of identifiable pathology using a combination of molecular genetics, chemogenetics and rodent models of visceral pain in both male and female subjects.

Scientific Focus Area: Neuroscience

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