Photobiomodulation as a Supportive Strategy for Botulinum Toxin-Related Complications: A Translational Perspective

Botulinum Toxin Type A (BoNT/A) has revolutionized clinical practice over the past three decades. Initially employed in neurology to manage strabismus and dystonias, it has since become one of the most frequently performed aesthetic procedures worldwide. By cleaving SNAP-25, a synaptic protein critical for acetylcholine release, BoNT/A induces temporary neuromuscular blockade, producing effects that last several months. This property underlies its therapeutic efficacy in conditions such as spasticity and migraine, as well as its widespread cosmetic use for reducing dynamic wrinkles. Although generally considered safe, adverse events are not uncommon. Clinical series report that between 1% and 6.5% of patients may experience complications, including eyelid ptosis, eyebrow or facial asymmetry, dysphagia, or excessive weakening of unintended muscles. While these effects are transient, they can cause functional limitations, psychological distress, and dissatisfaction with treatment outcomes. Currently, there are no evidencebased strategies to accelerate recovery from such complications. Management relies on reassurance, symptomatic support, or temporary pharmacological measures (e.g., apraclonidine eye drops for ptosis), while patients wait for spontaneous resolution as new SNAP-25 proteins are synthesized and axonal sprouting restores neuromuscular transmission. This therapeutic gap highlights the need for novel interventions capable of supporting neural and muscular regeneration in the aftermath of BoNT/A exposure. Photobiomodulation (PBM) has gained increasing attention as a safe, non-invasive modality with well-documented effects on mitochondrial bioenergetics, neuroplasticity, and tissue repair. By promoting synaptic remodeling, increasing neurotrophic signaling, and enhancing axonal regeneration, PBM offers a biologically plausible pathway to accelerate functional recovery in patients affected by BoNT/A complications. Recent translational discussions, including our contribution published in Life [1], propose PBM as a candidate intervention deserving systematic preclinical and clinical evaluation [2]. This perspective article aims to consolidate the mechanistic rationale, summarize supporting experimental evidence, and outline future directions for integrating PBM into the management of BoNT/A-related adverse effects.

Biological rationale and mechanisms

PBM involves red to near-infrared light absorption by cytochrome c oxidase in the mitochondrial respiratory chain, leading to increased ATP production, modulation of redox-sensitive signaling [3], and downstream activation of survival and plasticity pathways such as PI3K/Akt and MAPK/ERK. Preclinical studies have consistently shown that PBM can:
a) Upregulate neurotrophic factors such as BDNF and NGF.
b) Promote axonal sprouting and synaptogenesis.
c) Enhance SNAP-25 expression in nerve regeneration models.
d) Reduce inflammation and support neurovascular remodeling

These effects align with the biological requirements for recovery from BoNT/A-induced blockade, suggesting that PBM could accelerate the reestablishment of neuromuscular transmission once the toxin’s enzymatic activity subsides [4].

Evidence and translational perspectives

Experimental models in nerve injury, traumatic brain injury, and neurodegenerative diseases have demonstrated PBM’s ability to enhance structural and functional recovery. Importantly, PBM has shown beneficial effects on muscle fatigue and myonecrosis, further supporting its relevance in neuromuscular recovery [5]. However, it is critical to emphasize that no study has yet tested PBM in the specific context of BoNT/A-induced paralysis. The hypothesis remains unvalidated in both preclinical and clinical settings. While anecdotal reports suggest potential benefits in cases of iatrogenic ptosis, controlled trials are lacking. From a translational standpoint, PBM should be considered a supportive, time-dependent strategy rather than a direct antagonist to BoNT/A [6]. Its possible application window would begin once toxin activity declines, potentially accelerating synaptic reorganization and functional recovery [7].

Limitations and future directions

Several challenges must be addressed:
a) Specificity-BoNT/A acts through irreversible proteolysis of SNAP-25, a process PBM cannot reverse directly.
b) Dose-response-PBM exhibits biphasic effects [8], insufficient or excessive exposure may be ineffective or inhibitory.
c) Safety-Application in periorbital regions raises concerns regarding ocular safety.
d) Clinical gaps-No randomized controlled trials have evaluated PBM for BoNT/A complications.

Future research should begin with BoNT/A-specific animal models to establish optimal PBM parameters and intervention windows, followed by carefully designed pilot clinical studies.

Photobiomodulation emerges as a biologically plausible, safe, and non-invasive strategy that could support recovery from botulinum toxin type A (BoNT/A)-related complications. By targeting mitochondrial metabolism, upregulating neurotrophic pathways, and enhancing synaptic plasticity, PBM provides a mechanistic framework directly aligned with the processes required for neuromuscular restoration after BoNT/A-induced paralysis. Nevertheless, the current evidence remains preliminary and largely extrapolated from models of nerve injury, neurodegeneration, and muscle performance. To date, no experimental study has specifically evaluated PBM in the context of BoNT/A-induced synaptic blockade, and clinical data are limited to anecdotal observations. This gap underscores the urgent need for translational research, beginning with animal models of BoNT/A exposure, followed by rigorously designed clinical trials to establish safety, optimal parameters, and efficacy. If validated, PBM could represent not only a supportive tool to accelerate recovery from iatrogenic complications but also a paradigm shift in how clinicians approach adverse outcomes associated with BoNT/A. Its integration into clinical practice could improve patient satisfaction, reduce downtime, and expand the therapeutic armamentarium in both neurology and aesthetic medicine. By bridging mechanistic plausibility with clinical need, PBM highlights the value of translational science in addressing unmet challenges at the interface of technology and patient care.

1. Lopes RAB, Gonzalez LF, Gomes Silva S, Leonardo PS, Soncino C, et al. (2025) Photobiomodulation as a hypothetical strategy to reverse botulinum toxin effects: Exploring the neuro regenerative mechanisms and translational potential Life 15(8): 1206.
2. Rossetto O, Pirazzini M, Montecucco C (2014) Botulinum neurotoxins: Genetic, structural and mechanistic insights. Nat Rev Microbiol12(8): 535-549.
3. Jankovic J, Brin MF (1991) Therapeutic uses of botulinum toxin. N Engl J Med 324: 1186-1194.
4. Anders JJ, Lanzafame RJ, Arany PR (2015) Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg 33(4): 183-184.
5. Wang CZ, Chen YJ, Wang YH, Yeh ML, Huang MH, et al. (2014) Low-level laser irradiation improves functional recovery and nerve regeneration in a sciatic nerve crush rat model. PLoS One 9(8): e103348.
6. Cardoso FS, Serra FT, Coimbra NC, Gonzalez LF, Gomes SS (2022) Transcranial photobiomodulation changes neuronal morphology in the cerebral cortex of rats. Neurosci Lett 781: 136681.
7. Hamblin MR (2017) Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 4(3): 337-361.
8. Barrett DW, Gonzalez LF (2013) Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. Neuroscience 230: 13-23.