Steroid Route for Experimental Temporomandibular Joint Arthritis Treatment: Anti-Inflammatory Effects

Objectives: A significant number of juvenile idiopathic arthritis patients have inflammation within the temporomandibular joint (TMJ), possibly causing pain and decreased function. In this study, the anti-inflammatory effects of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting ability were evaluated after intra-articular and systemic delivery.
Methods: Twenty-four juvenile male Sprague-Dawley rats were divided into three equal treatment groups. In each group, experimental arthritis was induced with two unilateral intra-articular TMJ injections of complete Freund’s adjuvant (CFA) four weeks apart. During the second CFA injection: Group 1) intra-articular injection of 5 mg P-DEX, Group 2) intravenous tail vein injection of 15 mg P-DEX, or Group 3) nothing beyond the CFA injections. Four rats without any CFA injections were added as a control group. Animals were euthanized four weeks later. Skulls were stored in 10% formalin, decalcified in 5% formic acid, dissected to retain the head of the condyle, fossa and retrodiscal area and embedded in paraffin for hematoxylin and eosin histological evaluation. Retrodiscal inflammatory cells/connective tissues were evaluated using a grid-intersection point counting technique and digital software was used to determine the total area of inflammatory infiltrate. Groups were compared using analysis of variance.
Results: The inflammatory infiltrate was overwhelmingly lymphocytic, with 16.3 ± 1.3% of field in CFA alone versus no lymphocytes in unilateral controls (p<0.0001). Both TMJ P-DEX (10.1 ± 1.26%) and systemic P-DEX (9.0 ± 1.7%) reduced lymphocytes (p<0.002). Total area of inflammatory infiltrate was significantly less in the systemic injection group when compared to the group with CFA injections alone (2.55 ± 1.45mm² vs. 7.98 ± 1.26mm²; p=0.009) but not for intra-articular P-DEX (8.84 ± 1.19 mm²).
Conclusions: A single, high dose of systemic P-DEX was at least as effective as intra-articular P-DEX in reducing experimental TMJ arthritis inflammation.