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

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-1ß 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.

Variability in the Analgesic Response to Ibuprofen Is Associated With Cyclooxygenase Activation in Inflammatory Pain.

The mechanisms underlying interindividual variability in analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) are not well understood. Therefore, we performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars and were treated with ibuprofen (400 mg; N = 19) or placebo (N = 10). Analgesic efficacy was not associated with demographic or clinical characteristics, ibuprofen pharmacokinetics, or the degree of cyclooxygenase inhibition by ibuprofen. Compared with partial responders to ibuprofen (N = 9, required rescue medication within the dosing interval), complete responders (N = 10, no rescue medication) exhibited greater induction of urinary prostaglandin metabolites and serum tumor necrosis factor-α and interleukin 8. Differentially expressed genes in peripheral blood mononuclear cells were enriched for inflammation-related pathways. These findings suggest that a less pronounced activation of the inflammatory prostanoid system is associated with insufficient pain relief on ibuprofen alone and the need for additional therapeutic intervention.

Characterization and treatment of postsurgical dental implant pain employing intranasal ketorolac.

The intensity and duration of pain following surgical placement of dental implants has not been well studied. Thus, the aim of this open-label study was to characterize the nature of postsurgical pain following the placement of one to three implants. The secondary goal was to explore the analgesic efficacy and tolerability of intranasal ketorolac in this patient population. Following implant surgery, postoperative pain was rated moderate or severe in 25/28 patients (89 percent), requiring prn analgesic dosing for up to 3 days in 14/25 individuals (56 percent). Intranasal ketorolac displayed an analgesic onset within 20 minutes, a duration of at least 6 hours, and was well tolerated by the cohort with brief stinging of the nasal mucosa reported by 9/25 individuals (36 percent).

Double-blind, placebo-controlled, randomized pilot study of cerebral blood flow patterns employing SPECT imaging in dental postsurgical pain patients with and without pain relief.

BACKGROUND: Single-photon emission computed tomography (SPECT) has been employed in the study of altered regional cerebral blood flow (CBF) in experimental and chronic pain. CBF patterns have not been evaluated in patients with acute postoperative pain. OBJECTIVE: The purpose of this pilot study was to employ SPECT to measure CBF distribution associated with postoperative dental pain and to compare these CBF patterns to subsequent images in the same patients who were experiencing pain relief versus continued or worsening pain who had received active or placebo analgesic interventions. The primary outcome measure was the percentage change in blood flow in various regions of interest. METHODS: Twenty-two healthy individuals (10 males and 12 females, age range 20-29 years) who underwent the removal of ≥1 partial or full bony impacted mandibular third molars were evaluated for pain intensity as the local anesthesia dissipated, employing a 0 to10 numeric rating scale (0 = no pain; 10 = worst imaginable). When the subjects' pain level reached ≥4/10, they were injected intravenously with 260 MBq of technetium Tc 99m bicisate (ethyl cysteinate dimer). Under double-blind conditions and 10 minutes before being placed in the SPECT scanner, the first 10 subjects were randomized to receive intravenous ketorolac 15 mg or saline while the remaining 12 subjects were randomized to receive by mouth either ibuprofen 400 mg, ibuprofen 200 mg, acetaminophen 1000 mg, or placebo. One hour after drug administration, subjects were reevaluated for pain, injected with 925 MBq of technetium Tc 99m bicisate, given rescue medication if required, and then rescanned. CBF ratios were obtained for regions of interest and by normalizing to average whole brain activity. RESULTS: Subjects generally had a moderate degree (mean [SD], 7.3% [4.0%]) of thalamic asymmetry on initial scans with pain; after treatment, subjects reporting worsening pain regardless of the intervention had higher thalamic asymmetry (8.1% vs 2.8%) than those reporting relief of pain. Subjects who reported reduced pain after the intervention had significantly different (P < 0.05) mean CBF changes compared with those reporting worsening pain in the left prefrontal cortex, left sensorimotor area, right anterior cingulate, and right caudate. CONCLUSIONS: Acute postoperative dental pain was associated with moderate thalamic asymmetry that improved following successful pain management. Sustained or worsening pain was associated with increased CBF in brain regions associated with pain pathways, whereas pain relief was associated with decreased activity in the same areas.