Repeated exposure of naive and peripheral nerve-injured mice to a snake as an experimental model of post-traumatic stress disorder and its co-morbidity with neuropathic pain

Author(s)

Paschoalin-Maurin, Tatiana ^{[1, 2, 3]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Ophidiarium LNN FMRP USP INeC, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo FMRP USP, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, Ribeirao Preto Med Sch, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Behav Neurosci Inst INeC, Ave Cafe 2450, BR-14050220 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Brain Research; v. 1744, OCT 1 2020.
• Web of Science Citations: 0

Abstract

Confrontation of rodents by natural predators provides a number of advantages as a model for traumatic or stressful experience. Using this approach, one of the aims of this study was to investigate a model for the study of post-traumatic stress disorder (PTSD)-related behaviour in mice. Moreover, because PTSD can facilitate the establishment of chronic pain (CP), and in the same way, patients with CP have an increased tendency to develop PTSD when exposed to a traumatic event, our second aim was to analyse whether this comorbidity can be verified in the new paradigm. C57BL/6 male mice underwent chronic constriction injury of the sciatic nerve (CCI), a model of neuropathic CP, or not (sham groups) and were submitted to different threatening situations. Threatened mice exhibited enhanced defensive behaviours, as well as significantly enhanced risk assessment and escape behaviours during context reexposure. Previous snake exposure reduced open-arm time in the elevated plus-maze test, suggesting an increase in anxiety levels. Sham mice showed fear-induced antinociception immediately after a second exposure to the snake, but 1 week later, they exhibited allodynia, suggesting that multiple exposures to the snake led to increased nociceptive responses. Moreover, after reexposure to the aversive environment, allodynia was maintained. CCI alone produced intense allodynia, which was unaltered by exposure to either the snake stimuli or reexposure to the experimental context. Together, these results specifically parallel the behavioural symptoms of PTSD, suggesting that the snake/exuvia/reexposure procedure may constitute a useful animal model to study PTSD. (AU)

• FAPESP's process: 17/11855-8 - Study of corpus striatum and ventral mesencephalon endocanabinoid influence on neostriato-nigro-tectal GABAergic pathways during panic reactions of rodents threatened by venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 07/01174-1 - Study of the Involvement of opioid-, serotonergic- and noradrenergic-mechanisms of the pain endogenous inhibitory system in antinociceptive processes induced by oriented escape reactions evoked by chemical stimulation of the merdial hypothalamus
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/13398-2 - Investigation of chronic neuropathic pain and post-traumatic stress disorder comorbidity: role of glutamatergic, cannabinoid and vanilloid systems involving the prelimbic cortex and the periaqueductal grey
• Grantee: Joyce Mendes Gomes Tessari
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants