Maximal electroconvulsive shock-induced seizures elicit long-lasting analgesia and short-lasting hyperoxia in a sex dependent manner.

BACKGROUND

Following a seizure, both humans and non-human animals exhibit postictal analgesia; decreased perception of nociceptive stimuli. Despite several brain regions having been implicated in postictal analgesia, a convergent mechanism has not been determined. Previous studies have found that, following a seizure, there is a period of altered oxygen dynamics that is the mechanism for several seizure comorbidities. We examined oxygen dynamics in the locus coeruleus (LC) to determine its potential role in postictal analgesia.

METHODS

We employed maximal electroconvulsive shock (MES)-induced seizures to induce postictal analgesia, measured as increases in tail flick latency in mice. We assessed the effect of an MES-induced seizure on postictal oxygen levels in the LC using a surgically implanted oxygen-sensing probe. We used pharmacological interventions previously shown to prevent postictal hyperoxia to determine potential mechanisms of postictal hyperoxia in the LC following MES.

RESULTS

A single MES-induced seizure led to analgesia persisting until day 3 (48 h post-seizure) in females and day 5 (96 h post-seizure) in males, whilst hyperoxia in the LC lasted 15-20 min, mediated in part by CB1 receptors. This postictal analgesia was increased by 39-71% in females and 28-50% in males. We also observed a sex difference in the response to CB1 receptor antagonism, with a 93% decrease in the severity of hyperoxia in females and 50% increase in severity in males.

SIGNIFICANCE: Our results demonstrate that postictal analgesia following a single seizure persists much longer than previously described and is related to sex. Increased brain oxygenation in the LC following MES is relatively short-lived and is mediated in part by the activation of CB1 receptors in a sex-dependent manner.