Analgesic and Local Anesthetic Effects of a Clove-Derived Injectable Formulation via Modulation of Oxidative Stress...

The major bioactive constituent of Syzygium aromaticum (clove), eugenol, has been reported to possess analgesic and local anesthetic properties. However, direct evidence regarding the local anesthetic and antinociceptive effects of clove extract itself or its injectable formulations remains limited. Therefore, this study evaluated the neuroprotective, antinociceptive, and local anesthetic-like effects of S. aromaticum pharmacopuncture (SAP) using in vitro and in vivo models, with comparative assessment against lidocaine. Primary dorsal root ganglion (DRG) neurons were exposed to H₂O₂-induced oxidative stress and treated with SAP. Cell viability, neurite outgrowth, intracellular reactive oxygen species (ROS), and pain-related markers, including calcitonin gene-related peptide (CGRP), isolectin B4 (IB4), and substance P, were evaluated. In vivo analgesic and anesthetic effects, including CFA-induced inflammatory pain, were assessed using tail flick, von Frey, and hot plate tests in rat models. SAP significantly improved cell viability and promoted neurite outgrowth while attenuating oxidative stress-induced cellular damage. Additionally, SAP markedly suppressed intracellular ROS levels and decreased the expression of pain-related markers, including CGRP, IB4, and substance P. In vivo, high-dose SAP significantly increased tail flick latency, reaching cutoff levels comparable to those of 0.4% lidocaine. Furthermore, SAP attenuated mechanical hypersensitivity in the CFA-induced inflammatory pain model and reduced microglial activation, inflammatory mediators (cyclooxygenase-2, interleukin-1β), and nociceptive marker expression in DRG and spinal cord tissues. These findings provide experimental evidence supporting the antinociceptive and local anesthetic-like potential of SAP and highlight the involvement of oxidative stress modulation and nociceptive signaling in its pharmacological actions.