Inherited pain hypersensitivity and increased anxiety-like behaviors are associated with genetic epilepsy in Wistar Audiogenic Rats: Short- and long-term effects of acute and chronic seizures on nociception and anxiety

Author(s)

Lazarini-Lopes, Willian ; Silva-Cardoso, Gleice Kelli ; Cortes de Oliveira, Jose Antonio ; Correa Passos, Luiz Augusto ; Salgado, Andreia Ruis ; Rodrigues Demolin, Daniele Masselli ; Andrade Leite-Panissi, Christie Ramos ; Garcia-Cairasco, Norberto ; Coimbra, Norberto Cysne

• Document type: Journal article
• Source: Epilepsy & Behavior; v. 141, p. 13-pg., 2023-03-10.

Abstract

Anxiety and pain hypersensitivity are neurobehavioral comorbidities commonly reported by patients with epilepsies, and preclinical models are suitable to investigate the neurobiology of behavioral and neuropathological alterations associated with these epilepsy-related comorbidities. This work aimed to characterize endogenous alterations in nociceptive threshold and anxiety-like behaviors in the Wistar Audiogenic Rat (WAR) model of genetic epilepsy. We also assessed the effects of acute and chronic sei-zures on anxiety and nociception. WARs from acute and chronic seizure protocols were divided into two groups to assess short-and long-term changes in anxiety (1 day or 15 days after seizures, respec-tively). To assess anxiety-like behaviors, the laboratory animals were submitted to the open field, light-dark box, and elevated plus maze tests. The von Frey, acetone, and hot plate tests were used to mea-sure the endogenous nociception in seizure-free WARs, and postictal antinociception was recorded at 10, 30, 60, 120, 180 min, and 24 h after seizures. Seizure-free WARs presented increased anxiety-like behav-iors and pain hypersensitivity, displaying mechanical and thermal allodynia (to heat and cold stimuli) in comparison to nonepileptic Wistar rats. Potent postictal antinociception that persisted for 120 to 180 min was detected after acute and chronic seizures. Additionally, acute and chronic seizures have magnified the expression of anxiety-like behaviors when assessed at 1 day and 15 days after seizures. Behavioral analysis indicated more severe and persistent anxiogenic-like alterations in WARs submitted to acute sei-zures. Therefore, WARs presented pain hypersensitivity and increased anxiety-like behaviors endoge-nously associated with genetic epilepsy. Acute and chronic seizures induced postictal antinociception in response to mechanical and thermal stimuli and increased anxiety-like behaviors when assessed 1 day and 15 days later. These findings support the presence of neurobehavioral alterations in subjects with epilepsy and shed light on the use of genetic models to characterize neuropathological and behav-ioral alterations associated with epilepsy.(c) 2023 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 21/14198-3 - Epilepsies and neuropsychiatric comorbidities: characterization of cannabidiol and HUF-101 treatments in in vivo and in vitro experimental models os epilepsies
• Grantee: Willian Lazarini Lopes
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 21/13622-6 - Assessing anxiety and painful hypersensitivity as comorbidities associated with Epilepsy: effects of cannabidiol treatment and the role of CB1, TRPV1 and 5-HT1A receptors
• Grantee: Willian Lazarini Lopes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/15050-7 - Study of the role played by endocannabinoid and endovaniloid signalling in the pallidum on the activity of the neostriatum-pallido-nigral disinhibitory and nigro-tectal inhibitory pathways during the organization of innate fear of animals confronted to snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/14073-6 - Testing emotional vulnerability to threat in adults using a virtual reality paradigm of fear associated with autonomic variables
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/05957-8 - Epilepsies and neuropsyquiatric comorbidities: characterization of the effects of the treatment with cannabidiol and HUF-101 in in vivo and in vitro experimental models
• Grantee: Norberto Garcia Cairasco
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/06877-5 - Systemic treatment with canabidiol in a neuropathic pain model: evaluation of the sensorial-discriminative and emotional-motivacional components pain sensitivity
• Grantee: Gleice Kelli Ribeiro da Silva Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate