Section 4 of 5
Discussion
Carmen Lucia Kretiska Araujo, Graziele Silveira Fardin, Ana Paula Bernardi, Joane Severo Ribeiro, Ricardo Vitiello Schramm, Isadora Frois Ourique, Maria Luiza Santos, Betina Vescovi, Tássio Fernando Crusius, Flávia Marafon, Denis Valente, Níveo Steffen, Patricia Viana da Rosa, and Alessandra Peres · about 9 minutes
Despite the growing interest in the effects of photobiomodulation on inflammatory and oxidative processes, studies investigating the relationship between salivary biomarkers and clinical outcomes in abdominal surgery remain scarce. Salivary biomarkers have emerged as a promising tool for monitoring postoperative recovery, as they allow for the simultaneous assessment of local and systemic inflammatory responses. Their application has been well documented in oral and maxillofacial surgery, where salivary biomarkers provide insight into tissue healing and inflammatory modulation [27]. Furthermore, the non-invasive nature of saliva collection makes this approach particularly advantageous in populations for whom blood sampling may be challenging, such as pediatric or post-surgical patients with limited venous access [22]. This underscores the novelty and clinical relevance of the present study, as one of the few investigations applying salivary biomarker analysis to monitor recovery in abdominal aesthetic surgery.
Baseline TNF-α levels in both intervention and control groups were within or slightly below the reference ranges reported for healthy adults, indicating that participants were not markedly pro-inflammatory at baseline. Reported values in the literature vary considerably (22–47 pg/mL), reflecting methodological and population differences [6, 30]. In our study, mean TNF-α levels were at the lower end of this spectrum, supporting the absence of heightened inflammation preoperatively. The higher variability observed in the PBM group at the intermediate timepoint suggests heterogeneous individual responses to PBM. TNF-α values decreased slightly over time in both groups but remained within expected ranges, consistent with a normal resolution of inflammation after surgery. No significant between-group differences were observed.
IL-10, a key anti-inflammatory cytokine, presented elevated mean values across both groups, with consistently higher levels in the PBM group. This pattern suggests a postoperative compensatory response to surgical trauma, potentially enhanced by PBM. IL-10 is fundamental for regulating inflammation and promoting tissue repair [35, 36]. Previous reports indicate that PBM may stimulate IL-10 release, reducing inflammation and accelerating recovery [1]. In our study, however, no significant between-group differences were detected, possibly due to individual variability or limited PBM exposure. The wide dispersion of IL-10 values, particularly in the PBM group (IL-10 C = 12.87 ± 23.59 pg/mL), supports the notion of heterogeneous responses influenced by baseline inflammatory status or metabolic factors.
Although TNF-α and IL-10 values fluctuated within ranges considered normal for healthy adults, small changes may still reflect subtle immune modulation following abdominoplasty. However, the clinical sensitivity of these markers in detecting acute surgical inflammation requires further validation. Given that both TNF-α and IL-10 remained within normal ranges, their usefulness as salivary biomarkers for acute postsurgical monitoring may be limited, underscoring the need for cross-validation with serum levels in future studies.
In the present study, TBARS levels showed a reduction at 48 h postoperatively in the PBM group. However, this finding should be interpreted with caution. Although TBARS showed a statistically significant reduction at T1 in the unadjusted analysis, the very small effect size and the absence of significance after baseline adjustment indicate that this result should be interpreted carefully. This pattern may reflect biological variability as well as the exploratory nature of this pilot study. Nevertheless, the observed reduction in TBARS may be consistent with the antioxidant effects reported for PBM in experimental studies. Animal models of diabetes, arthritis, and high-intensity exercise have shown that PBM can reduce lipid peroxidation and enhance antioxidant defenses such as SOD, CAT, and GPx activities [12, 33]. Despite these findings, variability in TBARS assays and differences in PBM parameters, such as wavelength, energy density, and irradiation protocols, may contribute to heterogeneous outcomes across studies [32].
Although a statistically significant reduction in TBARS was observed, the clinical significance of this finding remains uncertain, as minimal clinically important difference (MCID) thresholds for salivary oxidative markers have not yet been established. Further clinical trials with standardized PBM protocols and larger sample sizes are needed to clarify the potential antioxidant effects of PBM during postoperative recovery.
Nitrite levels remained within reference ranges in both groups, with no significant temporal variation. Regression analysis revealed, however, that participants reporting regular physical activity in the preceding six months had significantly lower baseline nitrite levels (β = − 3.09; p = 0.047). This finding supports the hypothesis that exercise modulates nitric oxide metabolism by upregulating eNOS, enhancing vasodilation, and preserving vascular health [3, 39]. Physical activity also reduces oxidative stress, thereby maintaining NO bioavailability [5, 19]. The lower nitrite values in active participants may reflect more efficient NO turnover and reduced nitrite accumulation, consistent with cardiovascular benefits of regular exercise.
Although between-group differences did not reach clinical relevance (Cohen’s d = 0.04–0.36), this finding supports the interpretation that PBM and control groups exhibited largely comparable biomarker trajectories. The within-group reductions in TBARS showed small effect sizes, suggesting that although statistically significant, the magnitude of oxidative stress modulation was modest.
The use of saliva as a biological matrix for monitoring postoperative biomarkers also deserves consideration. Salivary biomarkers have increasingly been investigated as non-invasive indicators of systemic inflammation. Several circulating mediators can diffuse into saliva through transcellular or paracellular mechanisms in the salivary glands. Previous studies have demonstrated correlations between salivary and serum levels of inflammatory mediators and oxidative stress markers in various systemic conditions. However, most investigations have focused on oral or systemic diseases rather than postoperative responses following non-oral surgeries. Although saliva offers practical advantages such as non-invasive collection and suitability for repeated measurements, its sensitivity for detecting inflammatory changes after abdominal surgery remains uncertain. Salivary biomarkers may also be influenced by salivary flow rate, oral health status, and individual biological variability [15, 17, 9].
Pain intensity decreased significantly in both groups from T1 to T2. However, the PBM group consistently exhibited numerically lower pain scores, although this numerical difference did not translate into statistically significant between-group differences. Pain scores at both timepoints were strongly correlated (r = 0.64; p < 0.001), indicating stable perception during early recovery. The analgesic effects of PBM have been attributed to several biological mechanisms. These include modulation of inflammatory mediators, reduction of reactive oxygen species, stimulation of mitochondrial ATP production, promotion of angiogenesis and lymphatic drainage, and modulation of nociceptive pathways with endogenous opioid release []. Clinical studies in oral and maxillofacial procedures also support PBM as an adjunctive strategy for reducing postoperative pain, swelling, and functional impairment [2, 7, 13]. Variability in PBM parameters, however, remains a limitation for protocol standardization [8, 14, 24]. In contrast, postoperative pain reduction demonstrated large effect sizes in both groups (dz ≈ − 1.25), supporting its clinical relevance regardless of group allocation. This large within-group effect indicates a clinically meaningful reduction in pain, even in the absence of significant between-group differences.
While most PBM protocols in the literature involve multiple sessions, our study applied only a single session prior to discharge, mainly due to clinical feasibility in a surgical setting. This choice may have limited the potential cumulative or sustained effects of PBM. However, some clinical evidence suggests that a single session can also produce meaningful postoperative outcomes. For instance, Yüksek et al. [40] reported comparable effects between single and repeated sessions for pain, edema, and trismus after third molar extraction. Similarly, Tenore et al., [38] demonstrated significant pain reduction on days 0, 1, and 7 following a single intraoral and extraoral application. Roccon et al., [31] also found a single PBM session effective for symptom relief in Oral Lichen Planus, with an excellent safety profile. These findings support the rationale of testing a single-session approach in abdominoplasty, while future studies should evaluate repeated applications to better establish dose–response relationships and sustained benefits.
In addition to the use of a single PBM session, the energy delivered per irradiation site (3 J) may have represented a conservative dosing strategy for treating a large surgical area during a single postoperative session. This dose was selected to allow complete coverage of the surgical area within a clinically feasible treatment time before hospital discharge. It is possible that higher energies per irradiation site or repeated PBM sessions could produce more pronounced modulation of postoperative inflammatory and oxidative biomarkers. Therefore, future dose–response studies evaluating different energy levels and treatment schedules are warranted to determine the optimal PBM parameters for postoperative recovery.
The relationship between inflammatory/oxidative markers and postoperative pain perception is complex and multifactorial, involving both peripheral and central nociceptive mechanisms. In our study, Spearman correlations between inflammatory/oxidative markers and pain scores revealed no statistically significant associations, although moderate trends were observed for TNF vs. IL-10 and TBARS vs. pain. These trends suggest that inflammatory markers alone may not fully explain perceived pain or recovery dynamics. TBARS levels showed a non-significant trend toward association with pain scores, consistent with the hypothesis that oxidative stress may contribute to postoperative discomfort. The absence of statistically significant correlations may be related to the relatively small sample size and interindividual variability in inflammatory responses. Additional confounding factors, such as anesthetic regimen, analgesic protocols, and baseline health status, may also have influenced these results. Surgical trauma is known to increase oxidative stress through tissue injury, ischemia–reperfusion processes, and inflammatory activation, which may explain the relevance of monitoring lipid peroxidation markers such as TBARS during postoperative recovery [23].
Inflammation and oxidative stress are biologically plausible contributors to postoperative pain. However, their impact is also influenced by metabolic status, surgical technique, pharmacological management, and psychosocial factors. The lack of significant associations in this dataset highlights the multifactorial nature of postoperative pain and underscores the need for integrative approaches in future research. Studies with larger samples, multimodal biomarker panels, and standardized analgesic regimens will be essential to clarify mechanistic links between inflammation, oxidative stress, and pain in surgical recovery.
Taken together, these findings suggest that PBM may influence oxidative and inflammatory pathways during postoperative recovery. However, the magnitude and clinical relevance of these effects remain uncertain in the present pilot study.
Several methodological limitations must be acknowledged. The small sample size (n = 31) may have limited statistical power to detect subtle between-group differences or biomarker–pain associations. Additionally, the non-randomized design introduces potential selection bias, which may have influenced group comparability. Future randomized controlled trials are needed to minimize this source of bias. Biological variability, including age, comorbidities, and individual recovery responses, may have influenced biomarker levels and pain perception. The absence of a sham-irradiated control group is a limitation, as placebo effects cannot be excluded. Future trials should incorporate sham PBM to minimize bias. The three assessment timepoints may not fully capture the dynamic fluctuations in inflammatory and oxidative markers following surgery. Furthermore, variability in PBM application parameters and the limited number of sessions could have influenced treatment effects. Salivary biomarkers were not validated against serum levels in this study, which limits conclusions regarding their ability to fully reflect systemic inflammatory responses following non-oral surgical procedures such as abdominoplasty. Although saliva represents a convenient and non-invasive biological matrix, its biomarker concentrations may be influenced by local oral conditions, salivary flow rate, and individual biological variability [20, 26, 34]. Additionally, patient-reported outcomes were limited to pain assessment using the Visual Analog Scale. Other relevant dimensions of postoperative recovery, such as quality of life, patient satisfaction, functional recovery, and perceived wound healing, were not evaluated and should be considered in future studies. Additionally, the use of a single PBM session—while clinically pragmatic—may have limited the potential cumulative effects typically observed with repeated applications. Lack of prospective trial registration also limits transparency and reproducibility. To strengthen the evidence base, future studies should include randomized controlled trials with larger cohorts and standardized PBM protocols. Extended biomarker monitoring and validation of salivary biomarkers against serum measurements will also be important to clarify the clinical and mechanistic role of PBM in surgical recovery. No correction for multiple comparisons was applied due to the pilot design; therefore, marginal p-values should be interpreted with caution. This decision was maintained due to the exploratory nature of this pilot study, which aimed to identify preliminary trends to guide future controlled trials with larger samples and more robust statistical adjustment.