Occlusal Trauma Induces Neuroimmune Crosstalk for a Pain State

Author(s)

Abdalla, H. B. ^[1] ; Napimoga, M. H. ^[1] ; Trindade-da-Silva, C. A. ^[1] ; Guimaraes, M. ^[1] ; Lopes, M. ^[1] ; Dos Santos, V, P. C. ; Silva, W. A. Buarque E. ^[2] ; Silva, F. Andrade E. ^[2] ; Clemente-Napimoga, J. T. ^[1]

Affiliation

^[1] Inst & Ctr Pesquisas Sao Leopoldo Mand, Fac Sao Leopoldo Mand, Lab Neuroimmune Interface Pain Res, Campinas, SP - Brazil

^[2] Dos Santos, P. C., V, Univ Campinas UNICAMP, Piracicaba Dent Sch, Dept Prosthodont & Periodontol, Piracicaba, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF DENTAL RESEARCH; OCT 2021.
• Web of Science Citations: 0

Abstract

Temporomandibular joint (TMJ) disorder caused by occlusal trauma is one of the most controversial topics in dentistry. Experimental traumatic occlusion (ETO) induced by metal crowns cemented to mandibular first molars in rats causes a long-lasting nociceptive response. This study aimed to elucidate whether ETO generates an increase in inflammatory mediators in the TMJ. In addition, the impact of ETO on trigeminal ganglia, neurotransmitter release, and satellite glial cell (SGC) activation was investigated. ELISA revealed enhanced inflammatory mediators, including TNF-alpha, IL-1 beta, IL-6, CX3CL1, and ADAM-17 by Western blotting, in periarticular TMJ tissue after 28 d of ETO. In the trigeminal ganglia, ETO groups increased the release of the neurotransmitters substance P and glutamate. Overexpression of the AMPA receptor and upregulation of NMDA were observed in the 0.4- and 0.7-mm ETO groups, respectively, highlighting enhanced neuronal excitation. Increased IL-1 beta and COX-2 mRNA levels in the 0.7-mm ETO group confirmed trigeminal ganglia SGC activation. Immunofluorescence and electrophoresis of SGC revealed increased pERK expression in the 0.7-mm ETO group. ERK phosphorylation was shown to be nociceptive specific, with its upregulation occurring in cases of chronic inflammatory pain. Increased PKA mRNA levels were observed in the 0.4-mm ETO group, while CREB mRNA levels were upregulated for both ETO groups. Electrophoresis showed overexpression of sodium channel Nav 1.7 in the 0.7-mm ETO group, while immunofluorescence revealed that Nav 1.7 is expressed in sensory trigeminal ganglia cells. The results of this study suggest that occlusal trauma induces neuroimmune crosstalk, with synthesis of proinflammatory/pronociceptive mediators, which increases neuronal activity in trigeminal ganglia via the activation of an inflammatory response cascade to develop a persistent neuroinflammatory state that leads to central sensitization. (AU)

• 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
• 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