The beta-adrenergic receptors contribute to the beneficial effects of opioids in an experimental model of periodontal disease in rats

Cinthia Pacheco, Celso Queiroz-Junior, Kátia Maltos, Daniela Pacheco, Marcelo Caliari, Janetti Francischi. Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Opioids have shown anti-inflammatory and immunomodulatory effects. The mechanisms by which they produce such effects are various and include lower release of cytokines from leukocytes and stimulation of both hypothalamus-pituitary-adrenal axis and sympathetic nervous system. The aim of the present work was to investigate if the unspecific beta adrenergic receptor antagonist propranolol would reverse the effect of the opioid agonist morphine in decreasing the signs of periodontal disease (PD), an inflammatory condition of the teeth supporting tissues, using an experimental model in rats. To induce the disease a sterile silk ligature was placed around the second maxillary molar tooth of male Holtzman rats. Different groups of rats were injected with either propranolol (0.5-16mg/kg/day, s.c.) or sterile saline (s.c.) and 30 minutes afterwards with morphine (10mg/kg/day, s.c.), once a day, from the 3rd to the 5th day after ligature placement. Rats were killed by decapitation at day 11 and their maxillae were collected and prepared for histological analysis. Measurements of the main signs of PD, i.e. alveolar bone loss and collagen destruction, were obtained by morphometric analysis of histological sections stained by hematoxylin-eosin, through evaluation of the distances from the cemento-enamel junction to the alveolar bone crest or to the most coronal fiber attachment next to the affected teeth. The first signs of disease, i.e. alveolar bone loss and collagen destruction (expressed as mean±Standard Error of the Mean in mm), started on the fifth (0.40±0.08mm and 0.35±0.04mm, respectively) and were maximal at the 11th day after ligature placement (1.28±0.30mm and 1.02±0.20mm, respectively). Treatment of rats with Saline+Morphine significantly decreased alveolar bone loss and collagen destruction, 0.78±0.04mm and 0.60±0.03mm respectively, when compared to control animals, 1.31±0.15mm and 1.1 ± 0.1mm, respectively (p<0.05, one-way ANOVA followed by Student–Newman–Keuls post hoc test). Propranolol was able to completely reverse such beneficial effect of morphine, alveolar bone loss = 1.29 ± 0.27mm and fiber attachment loss = 0.86 ± 0.12mm, using the dose of 8 mg/kg/day. These results indicate that activation of beta-adrenergic receptors might be one of the mechanisms triggered by the opioid agonist to modulate periodontal disease.

Financial support: CNPq