<p>Neuropathic pain (NP) is a chronic pain syndrome caused by a lesion or disease of the somatosensory nervous system. It is characterized by complex clinical manifestations and limited therapeutic efficacy, markedly impairing quality of life. Traditional analgesics often show variable effectiveness, and are associated with significant adverse effects. To address these challenges in pain research, long non-coding RNAs (lncRNAs) have attracted interest due to their key roles in gene transcription, epigenetic regulation, and cellular signaling networks. LncRNAs can modulate multiple structures related to pain, including peripheral nerves, the spinal cord, and higher central nervous system regions, by regulating neuronal excitability, ion channel function, neuroinflammatory responses, glial cell activation, and synaptic plasticity. Notably, they may also participate in central mechanisms underlying the comorbidity of pain and emotional disorders. Nascent intervention strategies targeting lncRNAs, such as antisense oligonucleotides, RNA interference, gene editing, small molecule modulators, and lncRNA replacement therapy, are increasingly demonstrating therapeutic potential. However, constraints on potential clinical translation include limited species conservation of lncRNAs, high tissue and cell specificity, and challenges in delivery efficiency and long-term safety. LncRNAs provide novel molecular insights into NP mechanisms and offer significant opportunities for the development of precise analgesic strategies. Future studies should focus on cross-species validation, targeted delivery system optimization, and integrative mechanistic analyses, to advance clinical translation of lncRNA-based interventions.</p> Graphical Abstract <p></p>