Neuropathic pain (NP) is one of the most serious types of chronic pain, which is caused by a disease or injury affecting the somatosensory system(Alles and Smith, 2018). The prevalence of NP in the general population is about 7%–10%, which not only accounts for nearly a quarter of the number of patients with chronic pain but also exceeds the impact of chronic pain in terms of reduced quality of life and increased financial burden on patients(Bouhassira, 2019; Szewczyk et al., 2022). In addition to the characteristic symptoms of hyperalgesia, allodynia, and spontaneous pain, patients with NP may also interfere with physiological, psychological, and social well-being, which require early attention and treatment(Ma et al., 2020). Unfortunately, existing analgesic pharmacotherapies are of limited effectiveness and are often accompanied by side effects(Finnerup et al., 2021). This makes the treatment of NP very tricky, and there is an urgent need to find an effective drug to help many patients.

The pathogenesis of NP is complex, so the mechanism has not been elucidated, which brings great difficulty to the development of analgesic drugs. In recent years, RNA has become a popular research topic, including non-coding RNA (ncRNAs) in biology and medicine. ncRNAs include long non-coding RNAs (lncRNAs), microRNAs (miRNAs), small interfering RNAs (siRNAs), small nucleolar RNAs (snoRNAs), and piwi-interacting RNAs (piRNAs)(Caceres-Duran et al., 2020). Among them, the non-protein-coding transcripts longer than 200 nucleotides are called lncRNAs(Xie et al., 2023). Notably, lncRNAs may play a key role in NP by regulating the expression of pain-related genes through binding messenger RNAs (mRNAs) or miRNAs sponge mechanisms(Li et al., 2019; Tang et al., 2019; Yang et al., 2019). Combined with the role of traditional mRNA in the development of NP, the emergence of lncRNA may provide new ideas for drug development and mechanism exploration.

From the view of Chinese medicine theory, the main causes and pathogenesis of NP are Qi stagnation and blood stagnation. The rational use of traditional Chinese medicine (TCM) has the advantages of small adverse reactions, no dependence, costing less, and being easily prepared. Some studies have found that traditional Chinese medicine compounds or botanical active ingredients have good analgesic effects(Chen et al., 2023; Feng et al., 2020; Zhang et al., 2018). Shentong Zhuyu Decoction (STZYD) comes from Yi Lin Gai Cuo created by Qingren Wang of the Qing Dynasty (Nearly 200 years ago). STZYD consists of 12 Chinese herbs and is used to treat pain caused by blood stasis blocking the collaterals (Han et al., 2021; Jiang et al., 2022; Wang et al., 2021, Wang et al., 2021, Wang et al., 2021). According to the Chinese Pharmacopoeia 2020 (Chinese Pharmacopeia Commission: Pharmacopeia of the People's Republic of China. China Medical Science Press; Beijing, China, 2023), Ligusticum chuanxiong Hort. (Chuanxiong, CX), Prunus davidiana (Carr.) Franch. (Taoren, TR), Carthamus tinctorius L. (Honghua, HH) and Angelica sinensis (Oliv.) Diels (Danggui, DG) in the decoction has the effect of promoting blood circulation and removing blood stasis. However, no studies have yet reported the analgesic mechanism of STZYD in NP, so we hope to explore it in this study.

RNA-sequencing (RNA-seq) is the most widely used method, which can determine different classes of RNA expression changes in tissues under different conditions and be used to select candidate molecules at the gene level(Burke, 2017; Mendelevich et al., 2021). In this study, we hope to explore the analgesic mechanism of STZYD on NP animal models from the perspective of lncRNA-mRNA regulatory networks by RNA-seq technology.