200 Section - Comparative Effects of Manual and Mechanical Stimulation on Peripheral Regeneration and Central Neuroplastic Modulation After Facial Nerve Injury

Although Bell’s palsy generally shows a favorable natural recovery, up to one-third of patients experience incomplete restoration, persistent weakness, or synkinesis, underscoring the need for effective rehabilitation strategies. Consequently, clinicians frequently employ manual massage and soft-tissue mobilization as supportive treatments. However, despite their widespread use, no solid evidence validates their therapeutic benefit, and the underlying biological mechanisms remain unclear. Importantly, no prior study has systematically examined how tactile stimulation influences both peripheral nerve regeneration and central neuroplastic modulation after facial nerve injury. Filling this gap is essential, as rehabilitation techniques without mechanistic understanding cannot be optimized, standardized, or translated into evidence-based clinical practice.

Design: Rats underwent facial nerve axotomy and were allocated to four groups: sham, axotomy-only, manual stimulation, and mechanical stimulation (n=6 each). Manual stimulation involved gentle digital stroking; mechanical stimulation used a soft brush. Interventions were performed 3×/week for 8 weeks. Functional recovery was assessed by vibrissae movement and blink reflex. Electrophysiological reinnervation was quantified by electromyography (EMG). Peripheral regeneration was analyzed with transmission electron microscopy (TEM). Central responses in the brainstem facial nucleus were assessed via immunohistochemistry (ChAT, GFAP, Iba-1, Nissl) and Western blot (c-Jun, TLR2, SMAD2, p-AKT).

Results: Manual stimulation significantly enhanced recovery across all domains: fastest functional improvement, highest EMG amplitude, optimal myelin thickness and G-ratio on TEM, preserved motor neuron integrity (ChAT, Nissl), reduced neuroinflammation (GFAP, Iba-1, TLR2), suppressed injury markers (c-Jun, SMAD2), and maximally upregulated pro-survival pathways (p-AKT). Mechanical stimulation showed partial benefit; axotomy-only showed minimal recovery.

Conclusion: This study provides the first integrative evidence that manual stimulation robustly enhances both peripheral regeneration and central neuroplastic modulation in the brainstem facial nucleus, resulting in superior functional recovery with direct translational relevance for clinical facial paralysis rehabilitation.