A randomized, double-blind pilot study of analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen following dental implant placement surgery

Abstract

Introduction: Post-surgical pain following dental implant placement surgery is typically managed with non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. However, the comparative analgesic efficacy of over-the-counter doses of non-steroidal anti-inflammatory drugs and acetaminophen in implant patients is unknown. Therefore, we compared the analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen after surgical placement of one or two dental implants. Methods: Adult patients were treated with naproxen sodium (440 mg loading dose +220 mg q8h, n = 15) or acetaminophen (1,000 mg q6h-max daily dose 3,000 mg, n = 15) for 3 days after implant placement in a randomized, double-blind design. Pain was assessed on a 0-10 scale every 20 min for 6 h after study medication treatment. Tramadol (50 mg) was available as a rescue medication. Plasma and gingival crevicular fluid (GCF) were collected prior to the surgery and 0, 1, 2, 4, 6, 24, and 72 h after surgery for quantification of interleukin (IL)-6, IL-8, and IL-1β levels. Results: Pain scores were significantly lower in patients treated with naproxen sodium compared to those treated with acetaminophen. Inflammatory mediator levels in plasma and gingival crevicular fluid increased after surgery and returned to near baseline levels by 72 h. Plasma IL-6 levels were significantly lower 6 h after surgery in patients treated with naproxen sodium compared to acetaminophen. No differences in inflammatory mediator concentrations in gingival crevicular fluid were observed between the treatment groups. The number of implants placed and body mass index (BMI) influenced inflammatory mediator concentrations in plasma and gingival crevicular fluid, respectively. Discussion: Naproxen sodium was more effective than acetaminophen in reducing post-operative pain and systemic inflammation following surgical placement of one or two dental implants. Further studies are needed to determine whether these findings are applicable to more complex implant cases and how they affect clinical outcomes following implant placement. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04694300.

Keywords: analgesia; cytokine; dental implant; inflammation; non-prescription drugs; non-steroidal anti-inflammatory drugs; post-operative (post op) pain; prostaglandin.

FIGURE 1

Comparison of median pain scores at each pain assessment during (A) inpatient and (B) outpatient periods between patients treated with naproxen sodium (blue) and acetaminophen (orange). Error bars indicate interquartile range (*p < 0.05 for treatment).

FIGURE 2

Comparison of systemic and local inflammatory mediators between patients treated with naproxen sodium (blue) and acetaminophen (orange). (A) Plasma IL-6 concentrations over time by treatment. Data are shown as mean ± SEM (*p < 0.05 for time × treatment interaction). (B) Plasma IL-6 levels at T = 6 h expressed as percent change from baseline. Crossbars indicate median, and data are plotted on a log₁₀ scale (*p < 0.05; Mann-Whitney test). (C) IL-1β concentrations in gingival crevicular fluid (GCF) over time by treatment. Data are shown as mean ± SEM. (D) IL-8 concentrations in gingival crevicular fluid (GCF) over time by treatment. Data are shown as mean ± SEM.

FIGURE 3

Comparison of plasma IL-6 levels between patients treated with naproxen sodium (blue) and acetaminophen (orange) by number of implants. (A) Plasma IL-6 concentrations over time in patients receiving one implant. Data are shown as mean ± SEM. (B) Plasma IL-6 concentrations over time in patients receiving two implants. Data are shown as mean ± SEM. (C) Plasma IL-6 concentrations at T = 6 h by treatment and number of implants. Crossbars indicate median.

FIGURE 4

Comparison of IL-1β and IL-8 levels in gingival crevicular fluid (GCF) between patients with body mass index (BMI) < 25 kg/m² (blue) and BMI > 25 kg/m² (orange). (A) IL-1β concentrations in GCF over time. Data are shown as mean ± SEM (*p < 0.05 for BMI). (B) IL-1β concentrations in GCF at T = 24 h. Crossbars indicate median (*p < 0.05; Mann-Whitney test). (C) IL-8 concentrations in GCF over time. Data are shown as mean ± SEM (*p < 0.05 for BMI). (D) IL-8 concentrations in GCF at T = 24 h. Crossbars indicate median (*p < 0.05; Mann-Whitney test).