2022 MSC Poster Contest Presentation: Amygdala Kindling Alters Pain Sensitivity and Pain-Related Emotional Behaviours in Rats

Title: Amygdala kindling alters pain sensitivity and pain-related emotional behaviours in rats

Presenter: Evana Xiao, master’s student, Trent University, Canada

Methodology, findings and conclusions of the research
Our research aimed to investigate the experience of pain in individuals with epilepsy, however, the increased experience of fear and pain sensitivity is an issue that can be found with both epilepsy and migraine. To investigate this phenomenon, we used an animal model, amygdala kindling, that reproduces the changes that occur in the brain after repeated experience of seizures, creating a lowered threshold for excitability similarly found in migraine. We were particularly interested in the behavioural response to pain and the development of avoidance of pain. To study this, we used an aversive stimulus, specifically inflammatory pain, and created an association of the stimulus with one of two distinct chambers, referred to as the paired chamber. The other chamber, which was defined by the absence of the aversive stimulus, was referred to as the non-paired chamber. Aversion was determined by comparing the time spent in either compartment when the rat was allowed to roam freely between the two.

We found that seizure rats did not develop a significant avoidance of the formalin-paired chamber, while the controls did. Later examination of the medial prefrontal cortex suggested that the seizure rats had a diminished ability to respond to the stressor, which was further supported by indiscriminate hyperactivity between the two chambers as well as diminished overall pain behaviours. We were also able to confirm higher activity in the anterior cingulate cortex (ACC), a structure involved in facilitating the experience of pain, in seizure rats, indicating that seizure rats experience pain more intensely than non-seizure rats. We were able to negate this by inhibiting the ACC, producing analgesia accompanying a preference for the pain-paired chamber. Additionally, female rats developed a higher avoidance overall than the male rats did.

Overall, we found that seizure rats experience pain more intensely and strongly than non-seizure rats, and that seizure rats have more difficulty in managing their response to the painful stimulus. The results of this project open various avenues for investigation of the experience of pain and management of aversive stimuli in those whose brains are more susceptible to over-activity, such as those with migraines and seizures. The difference in the experience of pain in male versus female rats also provides interesting potential for the role of hormones in pain modulation and further research.

Implications of the research for understanding migraine and/or its comorbidities
The findings of this research provide insight into how pain is managed and how avoidance is developed in those whose cortical excitability is higher than normal, a state that can describe both those who experience migraines and those who experience seizures. Our research may also provide an avenue through which comorbid anxiety and panic disorders can be better understood since a characteristic of the amygdala kindling model is the production of fear and anxiety-related behaviours.