Experimental traumatic occlusion drives immune changes in trigeminal ganglion

Author(s)

Clemente-Napimoga, Juliana Trindade ; Mendes, Vagner ; Trindade-da-Silva, Carlos Antonio ; de Carvalho, Gustavo ; Paranhos, Aletheia Caldeira Goncalves Alcantara ; Silva, Frederico Andrade e ; Silva, Wilkens Aurelio Buarque e ; Napimoga, Marcelo Henrique ; Abdalla, Henrique Ballassini

• Document type: Journal article
• Source: International Immunopharmacology; v. 122, p. 9-pg., 2023-09-01.

Abstract

We previously demonstrated that experimental traumatic occlusion (ETO) induces a long-lasting nociceptive response. These findings were associated with altered neuronal patterns and suggestive satellite glial cell activation. This study aimed to elucidate the activation of satellite glial cells following ETO in the trigeminal ganglion. Moreover, we explored the involvement of resident and infiltrating cells in trigeminal ganglion in ETO. Finally, we investigated the overexpression of purinergic signaling and the CX3CL1/CX3CR1 axis. RT-qPCR and electrophoresis showed overexpression of GFAP in the trigeminal ganglion (TG), and immunohistochemistry corroborated these findings, demonstrating SGCs activation. ELISA reveals enhanced levels of TNF-& alpha; and IL-1 & beta; in TG after 28 d of ETO. In trigeminal ganglia, ETO groups improved the release of CX3CL1, and immunohistochemistry showed higher CX3CR1+ -immunoreactive cells in ETO groups. Immunohistochemistry and electrophoresis of the P2X7 receptor were found in ETO groups. The mRNA levels of IBA1 are upregulated in the 0.7mm ETO group, while immunohistochemistry showed higher IBA1+ -immunoreactive cells in both ETO groups. The expression of CD68 by electrophoresis and immunohistochemistry was observed in the ETO groups. For last, ELISA revealed increased levels of IL-6, IL-12, and CCL2 in the TG of ETO groups. Furthermore, the mRNA expression revealed augmented transcription factors and cytokines associated with lymphocyte activation, such as ROR & gamma;t, IL-17, Tbet, IFN & gamma;, FOXP3, and IL-10. The findings of this study suggested that ETO activates SGCs in TG, and purinergic signaling and CX3CL1/CX3CR1 axis were upregulated. We uncovered the involvement of a distinct subtype of macrophages, named sensory neuron-associated macrophage activation (sNMAs), and detected an expanded number of infiltrated macrophages onto TG. These findings indicate that ETO induces chronic/persistent immune response. (AU)

• FAPESP's process: 17/22334-9 - Use of drug delivery systems for the development and application of anti-inflammatory agents with potential immunomodulatory and neuroprotective effects
• Grantee: Marcelo Henrique Napimoga
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/04276-7 - The use of micro-needles coated with drugs for the control of pain and inflammation
• Grantee: Henrique Ballassini Abdalla
• Support Opportunities: Scholarships in Brazil - Post-Doctoral