eng Oriental Scientific Publishing Company Biosciences Biotechnology Research Asia 0973-1245 2026-06-22 23 2 59122 article Chandaraa Kumar Pandiyan 1 Narayanan Jaisankar 1 Chitra Vellapandian 1 Department of Pharmacology, Faculty of Medicine and Health Sciences, SRM Institute of Science and Technology, SRM College of Pharmacy, Kanchipuram, India Neuropathic pain is a chronic disease that occurs as a result of somatosensory damage, and is characterized by neuroinflammation, neuronal hyper excitability, and maladaptive plasticity. There is growing evidence that the Wnt signaling pathway is a key controller of these processes. Wnt3a mediates synaptic reorganization, glial activation, and release of pro-inflammatory cytokines via canonical Wnt/β-catenin signaling, and improves calcium influx, kinase activation, and central sensitization via non-canonical pathways, especially by Wnt5a and Ror2/Ryk receptors. In addition to neuropathic pain, abnormal Wnt signaling is also suggested to play a role in unexplored states of pain, such as visceral pain due to inflammation induced by obesity, cancer-related pain due to tumorigenic signaling, migraine vulnerability due to increased inhibitors like DKK1 and post-surgery pain because of fibrosis and compensatory repair. Anti-WNT3a/β-catenin (IWP-2, LGK974, XAV939), non-canonical, and anti-Ryk antibodies have demonstrated meaningful analgesic and neuroprotective effects in preclinical models. Taken together, these findings identify Wnt signaling as a dynamic mediator of pain sensitization and a compelling candidate for disease-modifying therapeutic strategies in neuropathic and chronic pain conditions. https://www.biotech-asia.org/vol23no2/the-role-of-wnt-pathways-in-neuropathic-and-underexplored-pain-conditions-from-mechanisms-to-treatment/ Canonical Wnt pathways; Neuropathic pain; Non-canonical Wnt pathway; Pain; Wnt signaling pathways β-catenin