Lidocaine inhibited ATP-induced currents in P2X7 subunits in a concentration-dependent manner.  (Image source: Thinkstock)

Lidocaine inhibited ATP-induced currents in P2X7 subunits in a concentration-dependent manner. (Image source: Thinkstock)

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Systemic lidocaine has several useful effects including the relief of chronic pain, and anti-inflammatory and antithrombotic actions. These diverse properties strongly suggest that mechanisms other than sodium channel blockade may be implicated in mediating the beneficial effects of lidocaine. Extracellular adenosine triphosphate (ATP) is a neurotransmitter acting through the ATP receptors P2X (ligand-gated ion channels) and P2Y (G-protein-coupled receptors). These receptors are widely distributed and are involved in many pathological conditions such as ischemia, inflammation, and pain.

Dr. Takafumi Horishita, Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Yahatanishiku, Kitakyushu, Fukuoka, Japan, and colleagues from the Departments of Occupational Toxicology and Pharmacology, together with colleagues from the Department of Molecular Pathology and Metabolic Disease, Tokyo University of Science, Noda, Chiba, Japan, and the Cancer Pathophysiology Division, National Cancer Center Research Institute, Chuouko, Tokyo, Japan, investigated the effects of lidocaine on purinergic receptors. Their results are discussed in the article titled “Lidocaine Preferentially Inhibits the Function of Purinergic P2X7 Receptors Expressed in Xenopus Oocytes,” which was published in this month’s issue of Anesthesia and Analgesia.

In a comprehensive study, the investigators found that lidocaine inhibited ATP-induced currents in P2X7 subunits in a concentration-dependent manner. Lidocaine had no inhibitory effects on P2X3 or P2X4 subunits. Although the inhibitory concentrations were greater than those found commonly with a systemic infusion, a local effect is possible. In contrast, mepivacaine, bupivacaine and ropivacaine had no inhibitory effects on the P2X7 receptor.

The researchers have shown a novel mechanism of action of lidocaine, which may in part explain its analgesic effects. It is salutary to note that one of the oldest local anesthetic drugs has important pharmacological properties that are not found with more modern agents. Lidocaine is still a key drug in modern anesthesia and pain medicine, and this study helps us to understand its mechanism of action.