The rostral ventromedial medulla modulates pain and depression-related behaviors caused by social stress

Autor(es)

Pagliusi, Marco ; Amorim-Marques, Anna P. ; Lobo, Mary Kay ; Guimaraes, Francisco S. ; Lisboa, Sabrina F. ; Gomes, Felipe V.

• Tipo de documento: Artigo Científico
• Fonte: Pain; v. 165, n. 8, p. 10-pg., 2024-08-01.

Resumo

Rostral ventromedial medulla (RVM) activation during social stress induces resilience to stress outcomes, including chronic pain and depression-related behaviors; inversely, RVM inhibition induces susceptibility to stress outcomes. The rostral ventromedial medulla (RVM) is a crucial structure in the descending pain modulatory system, playing a key role as a relay for both the facilitation and inhibition of pain. The chronic social defeat stress (CSDS) model has been widely used to study stress-induced behavioral impairments associated with depression in rodents. Several studies suggest that CSDS also causes changes related to chronic pain. In this study, we aimed to investigate the involvement of the RVM in CSDS-induced behavioral impairments, including those associated with chronic pain. We used chemogenetics to activate or inhibit the RVM during stress. The results indicated that the RVM is a vital hub influencing stress outcomes. Rostral ventromedial medulla activation during CSDS ameliorates all the stress outcomes, including social avoidance, allodynia, hyperalgesia, anhedonia, and behavioral despair. In addition, RVM inhibition in animals exposed to a subthreshold social defeat stress protocol induces a susceptible phenotype, facilitating all stress outcomes. Finally, chronic RVM inhibition-without any social stress stimulus-induces chronic pain but not depressive-like behaviors. Our findings provide insights into the comorbidity between chronic pain and depression by indicating the involvement of the RVM in establishing social stress-induced behavioral responses associated with both chronic pain and depression. (AU)

• Processo FAPESP: 20/08363-9 - Estudo de vias aferentes para o bulbo rostral ventromedial na modulação do comportamento do tipo depressivo e da hiperalgesia induzidos pelo estresse social em camundongos
• Beneficiário: Marco Oreste Finocchio Pagliusi Junior
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/19731-6 - Identificação de mecanismos epigenéticos induzidos por estresse que modulam a sinalização endocanabinóide e a resposta neuroimunológica como novos alvos farmacológicos no tratamento do transtorno de estresse pós-traumático (PTSD)
• Beneficiário: Sabrina Francesca de Souza Lisboa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/17597-3 - O impacto do estresse sobre o sistema dopaminérgico é determinado pelo período crítico de plasticidade: implicações para a depressão e a esquizofrenia e o estudo de novos alvos farmacológicos
• Beneficiário: Felipe Villela Gomes
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores