Morphometric assessment of gingival components under opioid exposure, after its withdrawal and pharmacological correction in an experiment

Natural and synthetic opioids are potent analgesic agents that are predominantly used for the management of acute and chronic pain syndromes. However, prolonged opioid exposure is accompanied by the development of dysbiotic and pathomorphological changes in the oral cavity and periodontium, characterized by the progression of inflammatory-dystrophic processes, impaired microcirculation, increased vascular permeability, deterioration of tissue oxygenation, and the development of sclerotic changes. Aim of the study – to investigate the dynamics of quantitative and qualitative changes in the components of the rat gingival mucosa under conditions of prolonged opioid exposure, after its withdrawal, and during pharmacological correction. The study was conducted on 58 adult male rats weighing 200 g, aged 4.5-7 months, which were divided into 5 groups: a control group and experimental groups. Animals of the experimental groups (II–V) were exposed to opioid administration and corrective interventions at different time points. Group II consisted of rats that received injections of the opioid analgesic nalbuphine in increasing doses (0.212-0.283 mg/kg) for 10 weeks. Group III animals received intramuscular nalbuphine (0.212-0.252 mg/kg) for 6 weeks, followed by a 4-week withdrawal period. Group IV rats received nalbuphine for 6 weeks, followed by a 4-week withdrawal period and pharmacological correction with pentoxifylline (2.86 mg/kg) and a 11-day course of the antibiotic ceftriaxone (2.86 mg/kg). In Group V, animals were administered the opioid analgesic for 10 weeks in escalating doses every two weeks (0.212-0.283 mg/kg), alongside pentoxifylline injections (2.86 mg/kg) for 6 weeks and ceftriaxone (2.86 mg/kg) for 11 days at the end of the experiment. Morphometric parameters were determined, including the thickness of the epithelium of the free gingiva and gingival sulcus, the height of connective tissue papillae, and the mean diameter of hemomicrovessels in the superficial vascular network of the rat gingival mucosa. Statistical analysis included normality testing via skewness and kurtosis coefficients, as well as the Shapiro-Wilk test. One-way analysis of variance (ANOVA) with Tukey’s post hoc test was used to determine statistically significant differences among three or more animal groups. The study demonstrated that the most pronounced changes in morphometric parameters were observed in animals subjected to 6-week opioid administration followed by a 4-week withdrawal without pharmacological correction. These changes indicated persistent structural alterations in gingival components and insufficient compensatory-adaptive mechanisms following cessation of opioid exposure. In animals receiving pentoxifylline and ceftriaxone after opioid withdrawal, complete restoration of morphometric parameters of gingival components was not achieved. However, a positive trend in tissue remodeling was observed compared with the group receiving 10-week opioid administration without correction. Administration of pentoxifylline and ceftriaxone under conditions of 10-week opioid exposure contributed to partial restoration of hemomicrocirculatory parameters in the lamina propria of the gingival mucosa. Thus, the results of this experimental study indicate that pentoxifylline and ceftriaxone contribute to stabilization of periodontal structural components and improvement of gingival mucosal status under conditions of prolonged opioid exposure and after its withdrawal.