Non-invasive Electrical Stimulation Upregulates Genes Encoding Melatonin-Related Machinery in Pineal and Salivary Glands, with Dermatome and Frequency-Specific Effects

Pineal Gland (PG) neuromodulation is possible via invasive, electrical stimulation of its sympathetic pathway. The present study aimed to investigate the potential of non-invasive neuromodulation of the pineal and salivary glands via electrical stimulation. Bilateral electrical stimulation at 10 or 80 Hz or sham stimulation was applied to either the C2 or T1 dermatomes of rats during the dark period for 2-hours. PG, salivary, and lacrimal glands were removed following stimulation and qPCR used to assess expression changes in genes associated with melatonin synthesis, regulation, and signalling. 80 Hz C2 dermatome stimulation significantly upregulated Hiomt within both the PG and submandibular glands, and Rarβ within PG only. 10 Hz C2 dermatome stimulation upregulated Mt3 within the submandibular gland, and both 10 and 80 Hz C2 dermatome stimulation upregulated Rorβ within the parotid gland. Expression was unchanged following 10 or 80 Hz T1 dermatome stimulation and no changes were found in the lacrimal gland following stimulation of either dermatome. Our findings demonstrated that non-invasive, electrical stimulation can modulate gene expression within both the PG and salivary glands with frequency- and dermatome-specific effects. The potential therapeutic effects of this neuromodulation modality need to be uncovered through further research.