Ortal Nachum, Shachar Zion Shemesh, Paz Kelmer, Itay Goor Aryeh, Lior Ungar
Facial hyaluronic acid (HA) injections are widely performed in aesthetic procedures, and their vascular complications are well recognized. In contrast, nonvascular neuropathic pain syndromes involving peripheral trigeminal nerve branches have received limited attention. In this study, the authors report a retrospective 4-patient case series of individuals evaluated at a tertiary headache and facial pain clinic for persistent facial pain or headache temporally associated with facial HA injections. Clinical assessment included injection history, symptom timing and evolution, anatomical pain distribution, focused neurologic examination, imaging when indicated, exclusion of alternative etiologies, and response to individualized treatment. The cases demonstrated heterogeneous peripheral trigeminal neuropathic phenotypes involving the infraorbital, infratrochlear, and supratrochlear nerve territories. Presentations included persistent trigeminal neuropathic pain, focal headache syndromes, and trigeminal neuralgia-like paroxysms. Two patients had infraorbital nerve involvement but distinct clinical manifestations, illustrating that injury or irritation of the same peripheral nerve may produce different pain phenotypes. All patients reported clinical improvement after individualized peripheral nerve-directed or local interventions, including hyaluronidase, targeted nerve blocks, pulsed radiofrequency, botulinum toxin, and neuropathic pain medications. These observations do not establish prevalence, causality, or treatment efficacy. However, they highlight the importance of careful procedural history, anatomical localization, exclusion of dental, otolaryngologic, central, and neurovascular causes, and early referral when symptoms persist. Prospective studies using standardized pain measures and targeted imaging are needed to define diagnostic criteria and management pathways. Level of Evidence: 4 (Therapeutic).