Radioprotective Effect of Lidocaine on Neurotransmitter Agonist-Induced Secretion in Irradiated Salivary Glands

Abstract

BackgroundPreviously we verified the radioprotective effect of lidocaine on the function and ultrastructure of salivary glands in rabbits. However, the underlying mechanism of lidocaine's radioprotective effect is unknown. We hypothesized that lidocaine, as a membrane stabilization agent, has a protective effect on intracellular neuroreceptor-mediated signaling and hence can help preserve the secretory function of salivary glands during radiotherapy.Methods and MaterialsRabbits were irradiated with or without pretreatment with lidocaine before receiving fractionated radiation to a total dose of 35 Gy. Sialoscintigraphy and saliva total protein assay were performed before radiation and 1 week after the last radiation fraction. Isolated salivary gland acini were stimulated with either carbachol or adrenaline. Ca2+ influx in response to the stimulation with these agonists was measured using laser scanning confocal microscopy.ResultsThe uptake of activity and the excretion fraction of the parotid glands were significantly reduced after radiation, but lidocaine had a protective effect. Saliva total protein concentration was not altered after radiation. For isolated acini, Ca2+ influx in response to stimulation with carbachol, but not adrenaline, was impaired after irradiation; lidocaine pretreatment attenuated this effect.ConclusionsLidocaine has a radioprotective effect on the capacity of muscarinic agonist-induced water secretion in irradiated salivary glands.

Is Pilocarpine Effective in Preventing Radiation-Induced Xerostomia? A Systematic Review and Meta-analysis

“…This phenomenon could be due to different mechanisms of salivary gland damage induced by radiation in different time phases. In the early phase after radiation, the main mechanism of xerostomia is attributable to plasma membrane damage, which could be prevented by pilocarpine or other specific receptor agonists (33). An in vivo study by Burlage et al (34) discovered that pilocarpine could increase proliferation of undamaged cells in the early phase when there was a sufficient number of remaining progenitor cells.…”

Radiation-Induced Oral Mucositis

“…Swishing and gargling the anesthetic viscous gel containing 2% lidocaine and holding 5 mL of it in mouth for 1 min then spitting it out before meals have been shown to be helpful for better alimentation (101). One clinical trial showed dyclonine hydrochloride to have a superior effect among all other agents without significant difference recorded (102).…”

“…Local anesthetics, e.g., diphenhydramine, viscous xylocaine, lidocaine, and dyclonine hydrochloride, are used for short-term relief of pain associated with RIOM, despite the fact that they can interfere with the taste sensation leading to hypoalimentation ( 99 , 100 ). Swishing and gargling the anesthetic viscous gel containing 2% lidocaine and holding 5 mL of it in mouth for 1 min then spitting it out before meals have been shown to be helpful for better alimentation ( 101 ). One clinical trial showed dyclonine hydrochloride to have a superior effect among all other agents without significant difference recorded ( 102 ).…”

Radiation-induced oral mucositis

“…Nevertheless, the preclinical studies xylocaine, lidocaine, and dyclonine hydrochloride, are used for short-term relief of pain associated with RIOM, despite the fact that they can interfere with the taste sensation leading to hypoalimentation (99,100). Swishing and gargling the anesthetic viscous gel containing 2% lidocaine and holding 5 mL of it in mouth for 1 min then spitting it out before meals have been shown to be helpful for better alimentation (101). One clinical trial showed dyclonine hydrochloride to have a superior effect among all other agents without significant difference recorded (102).…”