Garlic-derived bioactive components in neuropathic pain: molecular mechanisms and therapeutic promise.

Abstract

Neuropathic pain is a chronic condition associated with maladaptive changes in nociceptive pathways, driven by oxidative stress, mitochondrial impairment, neuroinflammation, ion channel dysfunction, and apoptotic dysregulation. Current pharmacological therapies often provide limited relief but with adverse effects highlighting the need for more safer therapeutic approaches. Garlic (Allium sativum) and its bioactive organosulfur compounds including allicin, S-allyl cysteine, diallyl disulfide, diallyl trisulfide have gained increasing attention for their neuroprotective potential. This review summarizes the mechanistic role of garlic-derived compounds in neuropathic pain modulation, focusing on their antioxidant, anti-inflammatory, anti-apoptotic, and mitochondrial-stabilizing properties. These bioactives regulate key signaling pathways such as NF-κB, Nrf2/HO-1, PI3K/Akt, and JNK, while also modulating TRPV1 and TRPA1 ion channels involved in nociception and central sensitization furthermore, garlic compounds enhance endogenous antioxidant defense, preserve mitochondrial bioenergetics, and inhibit caspase-mediated neuronal apoptosis, thereby contributing to neuroprotection. Despite promising preclinical evidence, challenges such as variability in garlic preparations, limited clinical studies, and insufficient pharmacokinetic data remain. Overall, garlic-derived compounds represent a promising complementary strategy for neuropathic pain management, warranting further standardized clinical investigations to validate their therapeutic efficacy and safety.