Abstract
Several factors might influence the duration and efficiency of local anesthesia. This study investigates the effect of habitual caffeine intake on lidocaine action and explores the potential involvement of voltage-gated sodium channels in the interaction effect. Wistar rats were divided into four groups: (i) control (Ctrl), (ii) lidocaine intraplantar injection (LIDO), (iii) habitual caffeine intake (CAF), and (iv) lidocaine intraplantar injection and habitual caffeine intake (LIDO + CAF). Behavioral assessments, consisting of a paw pressure test for mechanical pressure sensation and a paw withdrawal latency test for thermal pain sensation, were performed at 0, 30, 60, and 90 minutes following lidocaine injection and after 10, 11, and 12 weeks of CAF intake. Pressure sensation was significantly reduced in the LIDO + CAF group compared with the control group. Moreover, the LIDO + CAF group exhibited reduced sensation compared to LIDO alone group. The LIDO + CAF combination exerted a synergistic effect at 30 and 60 minutes compared with the control. This synergistic effect was noted at 60 minutes (11 weeks of CAF intake) and at 30 minutes (12 weeks of CAF intake) compared with LIDO alone. Augmented thermal pain-relieving effects were observed in the LIDO + CAF group at all weeks compared to the control group and at 10 weeks compared to LIDO alone group. The molecular analysis of dorsal root ganglia suggested that CAF upregulated the mRNA expression of the Nav1.3, Nav1.7, and Nav1.8 sodium channel subtypes. Chronic caffeine consumption potentiates the local anesthetic action of lidocaine in an experimental animal model through mechanisms that involve the upregulation of voltage-gated sodium channels in the dorsal root ganglia.
Highlights
Lidocaine is a classical local anesthetic agent and belongs to the amino amide class of local anesthetics
The combination group (LIDO + CAF) exhibited significant effects compared to the control at longer durations (30 and 60 minutes) in the 11th and 12th weeks of caffeine intake
Pain assessments were conducted by measuring the mechanical and thermal sensations after the application of pressure or heat stimuli that aggravate pain [13]. e findings from the present study revealed that the effects of lidocaine might be influenced by chronic caffeine intake. e improvement in the response to mechanical pressure stimulation was more prominent
Summary
Lidocaine is a classical local anesthetic agent and belongs to the amino amide class of local anesthetics. Lidocaine is indicated to eliminate pain sensation and discomfort by inhibiting the propagation and generation of action potentials in peripheral neurons through the blockade of sodium channels. E α-subunit of each channel identifies the members of sodium channels. Ese members are named Nav1.1 to Nav1.9 and have different expression patterns and physiological profiles. Voltage-gated sodium channel numbers 3 (Nav1.3), 7 (Nav1.7), and 8 (Nav1.8) are considered pain-related channels expressed in dorsal root ganglia [2]. Caffeine is a well-known natural compound present in various plant products. Caffeine is an integral component of several daily drinks, including tea, coffee, soft drinks, and energy drinks [3]. E consumption habits of these caffeinated drinks have facilitated the wide distribution of and Caffeine is an integral component of several daily drinks, including tea, coffee, soft drinks, and energy drinks [3]. e consumption habits of these caffeinated drinks have facilitated the wide distribution of and
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