The mechanism of dynamic switching between M1/M2 phenotypes of microglia in neuropathic pain: a narrative review

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Neuropathic pain (NeP) is a chronic pain disorder caused by damage to the somatosensory system, often presenting with long-lasting symptoms and limited efficacy of standard pharmacological treatments. Recent evidence indicates that the microglial activation exists on a dynamic and environment-dependent continuum and this plasticity critically influences the development and maintenance of neuropathic pain. During the polarization process, microglia can release different mediators, and these functional states dynamically regulate neuroinflammation and central sensitization, thereby exerting a profound impact on the occurrence and persistence of NeP. Among these phenotypes, dynamic functional transitions play a critical role in shaping pain outcomes. By releasing pro-inflammatory cytokines such as TNF-α and IL-1β, pain is intensified, whereas anti-inflammatory signaling contributes to protective and reparative effects. This review highlights the critical molecular mechanisms underlying microglial differentiation, including the P2X7, TLR4/NF-κB, and USP19/FOXO1 signaling pathways. It also discusses how these pathways influence the regulation of pain circuits. We also discuss intervention strategies targeting polarization balance, including the potential and challenges of emerging therapeutic approaches such as small-molecule inhibitors, biologics, natural products, and nano-deliver

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.