Abstract

Orofacial pain is a prevalent symptom in modern society. Some musculoskeletal orofacial pain is caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including emotional factors and alteration of the masticator muscle and temporomandibular joints (TMJs). TMJ inflammation is considered to be a cause of pain in patients with TMD. Extracellular proteolytic enzymes, specifically the matrix metalloproteinases (MMPs), have been shown to modulate inflammation and pain. The purpose of this investigation was to determine whether the expression and level of gelatinolytic activity of MMP-2 and MMP-9 in the trigeminal ganglion are altered during different stages of temporomandibular inflammation, as determined by gelatin zymography. This study also evaluated whether mechanical allodynia and orofacial hyperalgesia, induced by the injection of complete Freund's adjuvant into the TMJ capsule, were altered by an MMP inhibitor (doxycycline, DOX). TMJ inflammation was measured by plasma extravasation in the periarticular tissue (Evans blue test) and infiltration of polymorphonuclear neutrophils into the synovial fluid (myeloperoxidase enzyme quantification). MMP expression in the trigeminal ganglion was shown to vary during the phases of the inflammatory process. MMP-9 regulated the early phase and MMP-2 participated in the late phase of this process. Furthermore, increases in plasma extravasation in periarticular tissue and myeloperoxidase activity in the joint tissue, which occurred throughout the inflammation process, were diminished by treatment with DOX, a nonspecific MMP inhibitor. Additionally, the increases of mechanical allodynia and orofacial hyperalgesia were attenuated by the same treatment.

Highlights

  • Orofacial pain is a very common problem in modern society and is one of the primary reasons for seeking dental treatment in the general population

  • Several studies have reported that inflammation processes in the temporomandibular joints (TMJs) cause the production of proinflammatory substances, including tachykinins such as substance P and calcitonin gene-related peptides (CGRPs) [17]

  • Our results corroborate a study by Spears et al [17], in which the development of complete Freund’s adjuvant (CFA) inflammation of the TMJ was followed by variable increases in the concentration of inflammatory mediators in both the trigeminal ganglia (TG) and TMJ tissue

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Summary

Introduction

Orofacial pain is a very common problem in modern society and is one of the primary reasons for seeking dental treatment in the general population. Orofacial pain originates from conditions associated with hard and soft tissues of the head, face, neck, and all intraoral structures [1]. Musculoskeletal orofacial pain is sometimes caused by temporomandibular disorders (TMDs). This condition has a multi-factorial etiology, including alterations of the masticator muscle, temporomandibular joints (TMJs), and emotional factors [1]. TMJ-associated inflammation is considered to be one of the reasons for the pain reported by TMD patients [1,2]. Inflammation can occur in the synovial membrane (i.e., synovitis) or the capsule (i.e., capsulitis) and may result from local trauma, infection or degeneration, changes in collagen formation, or systemic polyarthritis, such as rheumatoid arthritis [3]

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