Comparative Evaluation of Puerarin and Lidocaine on the Excitability of Trigeminal Wide-Dynamic-Range Neurons: Potential for Orofacial Pain Management

Trigeminal neuralgia and orofacial pain often require effective local anesthesia with minimal side effects. Puerarin (PUE), a major bioactive flavonoid derived from Pueraria lobata, has shown potential analgesic properties. This study aimed to investigate the inhibitory effects of local PUE administration on the excitability of wide-dynamic-range (WDR) neurons in the spinal trigeminal nucleus caudalis (SpVc) and to compare its potency with the conventional local anesthetic lidocaine. Extracellular single-unit recordings were performed on SpVc WDR neurons in anesthetized rats. PUE (1 and 10 mM) or lidocaine (37 mM; 1%) was administered subcutaneously into the peripheral receptive field. Neuronal responses to graded non-noxious and noxious mechanical stimuli were quantified before and after drug application. Local administration of PUE significantly suppressed the mean firing frequency of SpVc WDR neurons in a dose-dependent and reversible manner. The inhibitory effect peaked at 10 min post-injection and recovered within 30 min. Notably, 10 mM PUE exerted an inhibitory magnitude (68.7 ± 6.4%) comparable to that of 37 mM lidocaine (58.1 ± 4.3%), indicating that PUE possesses approximately four-fold the inhibitory potency of lidocaine on a molar basis. The suppressive effect was consistent across both non-noxious and noxious stimulus intensities. These findings provide the first in vivo evidence that PUE effectively attenuates trigeminal nociceptive transmission, likely via the modulation of voltage-gated sodium channels and acid-sensing ionic channels at peripheral nerve terminals. As a natural dietary constituent with high potency and a low risk of systemic side effects, PUR represents a promising candidate for complementary and alternative medicine in the management of orofacial pain, such as temporomandibular disorders and trigeminal neuralgia.