MICRON-SIZED PEA MICROGRANULES AS AN ADJUNCTIVE STRATEGY FOR POSTOPERATIVE MANAGEMENT AFTER THIRD MOLAR EXTRACTION: A REAL-WORLD EXPERIENCE

V. Schweiger¹, F. Lonardi², A. Bertajola², A. Lerco², L. Villagrossi¹, A. Martini¹, C. Schievano³, E. Polati¹, M. Albanese² | ¹Department of Anaesthesia, Intensive Care and Pain Therapy, University of Verona, Verona, Italy; ²Department of Oral and Maxillofacial Surgery, University of Verona, Verona, Italy; ³Innovative Statistical Research, Padua, Italy

Introduction. Surgical extraction of third molars is one of the most common procedures in oral and maxillofacial surgery. Postoperative complications, including swelling, pain and trismus, are frequently reported and largely driven by tissue edema resulting from the inflammatory response to surgical manipulation (1). Palmitoylethanolamide (PEA) is an endogenous Autacoid Local Injury Antagonism (ALIA) lipid amide, produced on demand in response to tissue damage and contributing to restore local homeostasis, mainly through modulation of mast cell and microglia activity (2). In micron-sized formulations - i.e. micronized (mPEA) and ultramicronized (umPEA) - PEA shows increased bioavailability and represents a promising strategy for managing inflammation and pain. This real-world study evaluated the effect of microPEA as an adjunct to standard analgesics on postoperative edema and pain in patients undergoing third molar surgical extraction.
Methods. The study included 68 adult patients (≥18 years), of both sexes. During the postoperative week, all patients used analgesics as needed; 34 patients additionally received 2 sachets/day of orodispersible mPEA+umPEA granules (300 mg + 600 mg per sachet; Normast® MPS microgranules). Edema was assessed on postoperative days 3 (T3) and 7 (T7) using clinician-based photographic measurements. Pain severity was recorded daily (T1–T7) using a 0-10 Numeric Rating Scale (NRS), with patients classified at T1 as having absent-to-mild (NRS 0-4) or moderate-to-severe pain (NRS 5-10). Data were analyzed using a generalized linear mixed model (GLMM) with Tukey–Kramer post hoc tests for multiple comparisons. A P value <0.05 was considered statistically significant.
Results. At T3, edema was observed in 23/34 patients receiving standard analgesics alone and in 18/34 receiving additional microPEA. Over the following 4 days, edema decreased significantly more (P=0.001) in patients receiving microPEA (-77.0%) than in those receiving analgesics alone (-34.5%), as shown in Figure 1. Over the 7-day postoperative period, pain reduction differed significantly between treatment conditions as a function of pain severity (P=0.018), despite unrestricted use of as-needed analgesics in both groups. In patients with moderate-to-severe pain at T1, reduction was significantly greater in those receiving microPEA (-85%) than in those treated with analgesics alone (-71%) by T6 (P=0.027).
Conclusions. These findings suggest that microPEA supplementation may represent an effective adjunctive strategy for managing postoperative inflammation after third molar extraction. The greater reduction in edema compared with analgesics alone, together with enhanced pain relief in patients with moderate-to-severe pain, is clinically relevant. Given that edema is among the most troublesome postoperative symptoms, microPEA may improve overall postoperative recovery and contribute to better pain control, particularly in patients presenting with higher pain levels early after surgery.