Seizures Cause Long-Lasting Analgesia and Short-Lasting Hyperoxia

Background: After a seizure, humans with epilepsy and non-human animal models of seizures exhibit a decrease in nociceptive perception, hereafter called postictal analgesia. This alteration in nociceptive perception has previously been theorized to contribute to the commonality of injuries, such as burns, following a seizure. Despite previous studies implicating multiple brain regions and receptor types as playing a role in this phenomenon, its exact mechanism is currently unknown. Previous studies conducted in the Teskey lab have identified a prolonged period of hypoxia following a seizure – postictal hypoxia. I hypothesized that this hypoxic period would provide the mechanism of postictal analgesia. As most previous studies on postictal analgesia have been conducted using a chemoconvulsant model of seizure generation, I assessed the effectiveness of an alternate method of seizure generation, maximal electroconvulsive stimulation, as a model of postictal analgesia. I also examined brain oxygenation in the locus coeruleus – a region involved in the descending modulation of pain – before, during, and after maximal electroconvulsive stimulation-induced seizures. Methods: The nociceptive perception of mice before and after a seizure was measured using tail flick latency. The tail flick latency of each mouse was recorded prior to and following a maximal electroconvulsive stimulation-induced seizure on three days, each 48 hours apart. I examined the effect of a maximal electroconvulsive stimulation-induced seizure on postictal oxygen levels in the locus coeruleus using a surgically implanted oxygen-sensing probe to measure free oxygen levels in the region before, during, and after an MES-induced seizure in awake, freely moving mice. I also examined the effect of a COX-1 inhibitor (SC560) and a CB1 receptor antagonist (AM251) on postictal oxygen levels in the same region through the same oxygen-recording procedure, with the addition of administration of one of said drugs prior to seizure elicitation. Results: A single maximal electroconvulsive stimulation-induced seizure led to prolonged analgesia persisting for 48 hours in females and at least 96 hours in males. A single seizure also led to an acute period of hyperoxia in the locus coeruleus lasting approximately 15-20 minutes after the seizure. Administration of AM251 decreased this hyperoxia in females and increased it in males. Significance: This study increased our understanding of postictal analgesia, in that it persists long after what is typically considered the postictal period, and there is a sex difference in the duration of the change in nociceptive perception. This study also increased our knowledge of the effects of a seizure on brain oxygenation in the locus coeruleus – a single seizure results in hyperoxia that is mediated in part by the activation of CB1 receptors.

Name thesis:degree_name

Master of Science (MSc)

Discipline thesis:degree_discipline

Medicine – Neuroscience

Grantor

Cumming School of Medicine

Year dc:date.issued

2025

Author dc:creator

• Fick, Leah Janean

Advisor dc:contributor.advisor

• Teskey, Gordon Campbell

Committee members dc:contributor.committeemember

• Trang, Tuan
• Whelan, Patrick

• Epilepsy
• Seizure
• Pain
• Analgesia
• Hyperoxia
• Nociception
• Oxygen Dynamics
• Postictal Analgesia

Statement dc:rights

• Unless otherwise indicated, this material is protected by copyright and has been made available with authorization from the copyright owner. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

en

DOI

https://dx.doi.org/10.11575/PRISM/49678

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/122086