Mechanism of periocular acupuncture in alleviating dry eye neuropathic pain via regulation of the “periocular acupoint–trigeminal ganglion–ventral posteromedial thalamic nucleus” pathway

ObjectiveDry eye disease (DED) is a common ocular surface disorder characterized by tear film instability and trigeminal nerve-mediated corneal hyperesthesia. Periocular acupuncture has been demonstrated to relieve DED symptoms; however, the underlying mechanisms remain unclear. Thus, in this study, we aimed to investigate the therapeutic effect of periocular acupuncture on DED and its peripheral-central regulatory mechanisms.Materials and methodsA guinea pig model of dry eye neuropathic pain was established through subcutaneous injection of scopolamine hydrobromide combined with topical instillation of benzalkonium chloride solution. After 21 days, the model animals were treated with either periocular acupoint acupuncture (Acu) or non-acupoint acupuncture (NA). Dry eye-related parameters and ocular surface sensitivity indicators were measured. Histopathological changes in the ocular surface, lacrimal glands, and trigeminal ganglia (TG) were examined using hematoxylin–eosin staining, in vivo confocal microscopy, and transmission electron microscopy. Neural tracing was performed using Alexa Fluor 488 Cholera Toxin Subunit B (CTB-488) and Fluoro-Gold (FG) tracers, and patch-clamp recordings on ex vivo brain slices were utilized to assess the modulatory effects of periocular acupuncture on the excitability of ventral posteromedial thalamic nucleus (VPM) neurons.ResultsPeriocular acupuncture effectively improved dry eye symptoms and abnormal pain sensations. Additionally, it ameliorated lacrimal gland atrophy, reduced corneal epithelial compensatory hyperplasia and inflammatory cell infiltration, and improved the structural disorganization and pyknosis of the subbasal corneal nerve plexus and TG neurons. Neural tracing results revealed that the Acu group, particularly at TaiYang (EX-HN5) and JingMing (BL1) acupoints, specifically targeted the TG–VPM neural pathway, with significantly higher numbers of labeled neurons and stronger fluorescence intensity than the NA group (P < 0.01). Patch-clamp recordings demonstrated that periocular acupuncture suppressed the hyperexcitability of VPM neurons in the model group, as reflected by decreased action potential firing and increased rheobase.ConclusionOur results support the existence of a specific “periocular acupoint–TG–VPM” neural pathway, identify the pathological feature of VPM neuron hyperexcitability in dry eye neuropathic pain, and suggest that periocular acupuncture alleviates dry eye-related pain partially through regulating neuronal excitability. These findings provide experimental evidence for the clinical application.