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<p>Chronic pain is a pervasive condition affecting over 1.5 billion people globally; and imposes a significant financial and emotional strain on individuals and society. Despite advancements in treatment, current therapies often yield incomplete relief and may pose adverse effects, underscoring the need for novel approaches. Neuropilins (NRPs) transmembrane glycoprotein functioning as co-receptors for class 3 semaphorins and vascular endothelial growth factor (VEGF) family members have emerged as promising therapeutic targets. Neuropilin-1 (Nrp-1) is implicated in chronic pain via interactions with VEGF and transforming growth factor-beta (TGF-β), promoting macrophage migration and microglial reactivity. These interactions lead to the release of pro-inflammatory cytokines and contribute to astrogliosis and glial scar formation, which disrupt neuronal signaling and exacerbate chronic pain. Conversely, Nrp-1 alleviates pain through Sema3A binding, influencing neuronal plasticity and inhibiting pain pathways. This review underscores the multifaceted role of NRPs complex pathophysiology of chronic NRPs’ pain. NRPs emerge as critical players, influencing both inflammatory processes and neuronal modulation. Nanotechnology-based drug delivery systems show promise in targeting NRP receptors specifically, enhancing therapeutic efficacy and minimizing side effects. These systems utilize various carriers like liposomes, nanoparticles, and exosomes to deliver drugs directly to NRP-expressing cells. By strategically modulating NRP interactions and signaling pathways, it may be feasible to concurrently address both the inflammatory and neuronal components of chronic pain, potentially offering novel therapeutic avenues for the patients.</p>

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The underexplored role of neuropilins in chronic pain pathophysiology: a review

  • 期刊论文

  • 发表日期：

    2026年1月3日

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  • Nisha Sahu,
  • Deepak Chouhan,
  • Dilip Sharma,
  • Vinod Tiwari

摘要

Chronic pain is a pervasive condition affecting over 1.5 billion people globally; and imposes a significant financial and emotional strain on individuals and society. Despite advancements in treatment, current therapies often yield incomplete relief and may pose adverse effects, underscoring the need for novel approaches. Neuropilins (NRPs) transmembrane glycoprotein functioning as co-receptors for class 3 semaphorins and vascular endothelial growth factor (VEGF) family members have emerged as promising therapeutic targets. Neuropilin-1 (Nrp-1) is implicated in chronic pain via interactions with VEGF and transforming growth factor-beta (TGF-β), promoting macrophage migration and microglial reactivity. These interactions lead to the release of pro-inflammatory cytokines and contribute to astrogliosis and glial scar formation, which disrupt neuronal signaling and exacerbate chronic pain. Conversely, Nrp-1 alleviates pain through Sema3A binding, influencing neuronal plasticity and inhibiting pain pathways. This review underscores the multifaceted role of NRPs complex pathophysiology of chronic NRPs’ pain. NRPs emerge as critical players, influencing both inflammatory processes and neuronal modulation. Nanotechnology-based drug delivery systems show promise in targeting NRP receptors specifically, enhancing therapeutic efficacy and minimizing side effects. These systems utilize various carriers like liposomes, nanoparticles, and exosomes to deliver drugs directly to NRP-expressing cells. By strategically modulating NRP interactions and signaling pathways, it may be feasible to concurrently address both the inflammatory and neuronal components of chronic pain, potentially offering novel therapeutic avenues for the patients.