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The interplay of social isolation, sex, and hyperalgesic priming on behavior and hormone levels in a mouse model

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Autor(es):
Baptista-de-Souza, Daniela ; Oliveira, Melissa Kessia Cavalcante ; Braga-Dias, Ana Claudia ; Otero, Silvia Jimena Cardenas ; Carneiro, Natalia Urel ; Avalo-Zuluaga, Julian Humberto ; Canto-de-Souza, Lucas ; Crestani, Carlos C. ; Nunes-de-Souza, Ricardo Luiz
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: Physiology & Behavior; v. 305, p. 13-pg., 2025-12-02.
Resumo

Chronic pain profoundly impacts mental health, and the social environment significantly modulates pain perception and emotional states. Recognizing the influence of biological sex on pain modulation, basic pain research increasingly investigates sex differences. The hyperalgesic priming protocol effectively models the neuroplastic mechanisms underlying the transition from acute to chronic pain in male and female rodents. Furthermore, accumulating evidence implicates specific hormones, including oxytocin, vasopressin, and corticosterone, in the pathophysiology of pain. This study aimed to determine the interactive influence of sex and social isolation on pain-related behaviors and plasma levels of oxytocin, vasopressin, and corticosterone in mice subjected to hyperalgesic priming. Two experiments were conducted using adult male and female mice (60-63 postnatal days). Experiment 1 assessed mechanical hypersensitivity, facial expression, and anxiety- and depression-like behaviors. In Experiment 2, following a period of social isolation, mice were euthanized, and blood samples were collected via cardiac puncture for plasma hormone analysis. Our results revealed that social isolation impaired recovery from mechanical hypersensitivity and increased facial expressions of pain, specifically in female mice. Independent of sex and hyperalgesic priming, isolation produced heightened anxiety- and depression-like behaviors. Hormonal analyses demonstrated sex-specific effects of isolation. Plasma oxytocin levels decreased upon isolation in both male and female mice. Curiously, primed isolated males showed a recovery of oxytocin levels similar to na & iuml;ve mice, whereas primed isolated females maintained significantly lower oxytocin levels. Social isolation, coupled with hyperalgesic priming, also decreased vasopressin levels in females. While males displayed higher baseline vasopressin levels, isolation and/or hyperalgesic priming led to a reduction in their plasma vasopressin compared to na & iuml;ve groups. Curiously, social isolation decreased of corticosterone levels in both males and females. In conclusion, our findings demonstrate that social isolation differentially modulates behavioral and hormonal responses to hyperalgesic priming in a sex-dependent manner, highlighting the complex interplay between social environment, sex, and pain chronification. (AU)

Processo FAPESP: 23/01341-8 - Avaliação do papel do complexo amidaloide, hipocampo dorsal e a influência do sexo e a idade sobre respostas relacionadas à depressão em camundongos submetidos ao estresse de testemunho da derrota social
Beneficiário:Julian Humberto Avalo Zuluaga
Modalidade de apoio: Bolsas no Brasil - Mestrado
Processo FAPESP: 24/05877-2 - Papel do dimorfismo sexual e análise dos efeitos comportamentais e neuro-funcionais após o tratamento com ocitocina em camundongos submetidos ao modelo de hyperalgesic primming
Beneficiário:Natália Urel Carneiro
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 24/01917-0 - Investigação das projeções e estimulação quimiogenética de neurônios ocitocinérgicos sobre os componentes sensorial e afetivo-emocional da dor em camundongos machos e fêmeas submetidos ao modelo de hyperalgesic primming
Beneficiário:Ana Claudia Braga Dias
Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 22/06260-3 - Avaliação de lateralização funcional no controle das respostas cardiovasculares e comportamental ao medo condicionado ao contexto pelo córtex pré-frontal medial em ratos
Beneficiário:Carlos Cesar Crestani
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 22/04387-6 - Impacto do dimorfismo sexual e da neurotransmissão ocitocinérgica sobre a dor crônica em modelos animais e em humanos
Beneficiário:Daniela Baptista de Souza
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 23/13491-4 - Impacto do dimorfismo sexual e da neurotransmissão ocitocinérgica sobre a dor crônica em modelos animais e em humanos
Beneficiário:Daniela Baptista de Souza
Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores