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

• Published in: Journal of cellular physiology Vol. 236; no. 9; pp. 6571 - 6580
• Main Authors: Nascimento, Glauce C., De Paula, Bruna B., Gerlach, Raquel F., Leite‐Panissi, Christie R. A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2021
• Subjects: Amygdala; Amygdala - metabolism; Animals; Astrocytes - metabolism; Blood-brain barrier; Chronic pain; Extracellular matrix; Facial Pain - complications; Freund's Adjuvant; Gelatin - metabolism; Gelatinases - metabolism; Glial fibrillary acidic protein; Hypothalamus; Immunofluorescence; Inferior colliculus; Inflammation; Inflammation - pathology; Inhibition (psychology); limbic system; Limbic System - enzymology; Limbic System - pathology; Male; Matrix metalloproteinase; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinases; metalloproteinases; orofacial pain; Pain; Periaqueductal gray area; Rats; Rats, Wistar; Superior colliculus; Temporomandibular joint; Temporomandibular Joint - enzymology; Temporomandibular Joint - pathology; Temporomandibular Joint Disorders - enzymology; Temporomandibular Joint Disorders - pathology; Therapeutic targets; Up-Regulation; orofacial pain; metalloproteinases; limbic system; inflammation; extracellular matrix
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.30341

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. Extracellular matrix metalloproteinases in specific limbic regions contribute to the development and maintenance of inflammatory orofacial pain. Temporomandibular inflammation induces an increased MMP‐2 and ‐9 expression and activity in the limbic structures in time and spatial dependent manner. There is a co‐localization of MMP‐2 and MMP‐9 with astrocyte cells during persistent temporomandibular inflammation that could suggest one of the sources for limbic gelatinolytic production experimental condition.