Acanthoscurria gomesiana spider-derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid

Autor(es)

Medeiros, Ana Carolina ; Medeiros, Priscila ; Ruggiero, Rafael Naime ; De Gregorio, Danilo ; Gobbi, Gabriella ; Silva Jr, Pedro Ismael ; dos Santos, Wagner Ferreira ; Coimbra, Norberto Cysne ; de Freitas, Renato Leonardo

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY; v. 37, n. 7, p. 14-pg., 2023-04-17.

Resumo

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comorbidity in rats. To investigate that comorbidity, neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. The biotinylated biodextran amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study brain connections. Rodents were further subjected to von Frey (mechanical allodynia), acetone (cold allodynia), and forced swim (depressive-like behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the periaqueductal gray matter (dPAG) and the dorsal raphe nucleus (DRN). Neuronal activity of DRN neurons decreased in CCI rats. However, PrL cortex treatment with Mygalin increased the number of spikes on DRN neurons. Mygalin treatment in the PrL cortex decreased both mechanical and cold allodynia and immobility behavior in CCI rats. PrL cortex treatment with N-methyl-D-aspartate (NMDA) receptor receptors attenuated the analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin administration into the PrL increased the activity of DRN neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the NMDA agonist reversed these effects. (AU)

• Processo FAPESP: 14/11869-0 - EMU concedido no processo 2013/12916-0: aparelho para a neuroestimulação DBS (Thomas mini matrix system - Thomas recording GmbH® - winchester Strasse - Giessen - Germany)
• Beneficiário: Renato Leonardo de Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 13/12916-0 - Participação dos circuitos endocanabinóides, glutamatérgicos e endovanilóides do córtex pré-frontal medial no modelo de dor neuropática e da investigação das comorbidades dor crônica e outras desordens neurológicas
• Beneficiário: Renato Leonardo de Freitas
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores