Temporomandibular inflammation regulates the matrix metalloproteinases MMP‐2 and MMP‐9 in limbic structures

Abstract

Temporomandibular disorder (TMD) is characterized by acute or chronic orofacial pain, which can be associated with inflammatory processes in the temporomandibular joint (TMJ) and emotional disorders. Peripheral and central sensitization in painful orofacial processes is common, and it can be triggered by peripheral inflammatory challenge with consequent neuroinflammation phenomena. Such neuroinflammation comes from inflammatory products from supportive cells, blood-brain barrier, and extracellular matrix. Here, we evaluated the possible recruitment of limbic structures for modified matrix metalloproteinases (MMPs) expression and activity during temporomandibular inflammation-induced orofacial persistent pain. The inflammatory process in TMJs of rats was induced by Freund's Complete Adjuvant (CFA) administration.The activity and expression of MMPs-2 and 9 were assessed by in situ zymography and conventional zymography, respectively. A glial colocalization with the MMPs was performed using immunofluorescence. The results evidenced both short-and long-term alterations on MMP-2 and -9 expression in the limbic structures following CFA-induced temporomandibular inflammation. The gelatinolytic activity was increased in the central amygdala, hippocampus, hypothalamus, ventrolateral periaqueductal gray (vlPAG), superior colliculus, and inferior colliculus. Finally, an increase of colocalization of MMP-2/GFAP and MMP-9/GFAP in CFA-induced inflammation groups was observed when compared with saline groups in the central amygdala and vlPAG. It is possible to suggest that glial activation is partly responsible for the production of gelatinases in the persistent orofacial pain, and it is involved in the initiation and maintenance of this process, indicating that inhibition of MMPs might be pursued as a potential new therapeutic target for TMD.

The Influence of the COVID-19 Pandemic on the Stress Levels and Occurrence of Stomatoghnatic System Disorders (SSDs) among Physiotherapy Students in Poland

“…As a consequence, symptoms such as: bruxism, pain in the temporomandibular joints (TMJs), and headaches may appear. Long-term symptoms of SSDs may contribute to irreversible changes in this system, resulting in impaired chewing, swallowing, speech, and breathing functions [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Additionally, long-term reports about TMJ internal derangements were released [21][22][23][24][25].…”

Glia and Orofacial Pain: Progress and Future Directions

“…upregulation) [25][26][27] −  GFAP [28][29][30][31] − Release pro-inflammatory mediators [28] −  Gap junction function [28] − Increase neuronal activity (Nav1.7 and pNR1 upregulation) [28,30] o  Iba1/CD11b [32,33] o Release pro-inflammatory mediators [34] Carrageenan injection in the TMJ ND ND ND −  Iba1 [35] Zymosan injection in the TMJ ND ND ND − Iba1 [35] Capsaicin injection in the TMJ ND − S100B [36] − Gap junction function [36,37] ND ND − Release of inflammatory mediators [21] TMD CFA injection in the TMJ ND − GFAP [22][23][24] − Release pro-inflammatory mediators [22,25,26] − Gap junction function [22] −  neuronal activity (Nav1.7 upregulation) [25][26][27] −  GFAP [28][29][30][31] − Release pro-inflammatory mediators [28] −  Gap junction function [28] − Increase neuronal activity (Nav1.7 and pNR1 upregulation) [28,30] o  Iba1/CD11b [32,33] o Release pro-inflammatory mediators [34] Carrageenan injection in the TMJ ND ND ND −  Iba1 [35] Zymosan injection in the TMJ ND ND ND − Iba1 [35] Capsaicin inje...…”

“…− Not activated [42] Dental pulp injury − Release of inflammatory mediators [21] TMD CFA injection in the TMJ ND − GFAP [22][23][24] − Release pro-inflammatory mediators [22,25,26] − Gap junction function [22] −  neuronal activity (Nav1.7 upregulation) [25][26][27] −  GFAP [28][29][30][31] − Release pro-inflammatory mediators [28] −  Gap junction function [28] − Increase neuronal activity (Nav1.7 and pNR1 upregulation) [28,30] o  Iba1/CD11b [32,33] o Release pro-inflammatory mediators [34] Carrageenan injection in the TMJ ND ND ND −  Iba1 [35] Zymosan injection in the TMJ ND ND ND − Iba1 [35] Capsaicin injection in the TMJ ND − S100B [36] − Gap junction function [36,37] ND ND…”

“…Capsaicin injection in the TMJ ND − S100B [36] − Gap junction function [36,37] ND ND − p38MAPK inhibitors reduce central sensitization [44] Pulp exposure followed by CFA application ND − − Release of inflammatory mediators [21] njection in the TMJ ND − GFAP [22][23][24] − Release pro-inflammatory mediators [22,25,26] − Gap junction function [22] −  neuronal activity (Nav1.7 upregulation) [25][26][27] −  GFAP [28][29][30][31] − Release pro-inflammatory mediators [28] −  Gap junction function [28] − Increase neuronal activity (Nav1.7 and pNR1 upregulation) [28,30] o  Iba1/CD11b [32,33] o Release pro-inflammatory mediators [34] geenan injection in the TMJ ND…”

“…Chronic pain is associated with functional, structural plasticity and reorganization of the pain circuits [166]. Glial plasticity has been shown in the thalamus, the descending modulatory pathway as well as the limbic systems in a few orofacial pain conditions [8,31,[170][171][172][173][174]. How glial cells modulate neuronal plasticity both functionally and structurally and their role in the organization of pain circuits at different disease states remains a daunting task in the orofacial pain field.…”