Neuropathic pain (NP), pain directly caused by a lesion or disease affecting the somatosensory system, is a common clinical problem that typically presents as persistent pain (burning, squeezing, pressure) or paroxysmal pain (shock like sensation, stinging), evoked (brush, pressure, cold), or anesthetic and paresthe (tingling, pins and needles) sensation (Finnerup et al., 2021). The reasons for the development of NP are multifaceted, and the International Association for the study of pain considers NP to originate from or be caused by dysfunction of the nervous system, which is clinically mainly seen by injury to the central or peripheral nerves, inflammation, infection, diabetes, and tumor compression, among others (Szewczyk et al., 2022). Despite intense efforts to address this issue, research progress on the molecular mechanisms and therapeutic approaches to NP has so far remained limited. Therefore, NP is widely regarded as one of the most difficult to treat pain syndromes, and its adverse consequences for patients may lead to severe socioeconomic effects.

LncRNAs are a kind of long non-coding RNA, more than 200 nucleotides in length, which are highly expressed throughout the cell cycle and play an important regulatory role in every stage of gene expression. Recent studies have shown that lncRNAs play an important role in the formation of NP by up - or down-regulation of expression in NP models (Jiang et al., 2022). The aberrant expression of lncRNAs in NP has attracted much attention, and many lines of research evidence also support lncRNAs as novel therapeutic targets for the treatment of NP. Studies have identified lncRNAs involved in NP such as MALAT1 (Wu et al., 2020), MEG3 (Dong et al., 2021), H19 (Meng et al., 2022), P21 (Liu et al., 2021), PVT1 (Zhang et al., 2021) and so on. The lncRNA PCat19 is located at 19q13.2, which plays a tumor activating role as a pro-oncogene has been demonstrated in a variety of cancer species. For instance, lncRNA PCAT19 is activated by SP1 and acts as an oncogene in gastric cancer by competitively binding to miR429 to up-regulate DHX9 expression and thus promote tumor development (Xiao et al., 2022). Xu et al. (2019) demonstrated that lncRNA PCAT19 promotes laryngeal cancer cell proliferation and tumorigenesis by targeting the miR-182/PDK4 axis to regulate metabolic homeostasis. Zhang et al. (2019) displayed that PCAT19 views the p53 tumor suppressor pathway as a target gene to negatively regulate p53 expression, which in turn promotes cancer cell proliferation in non-small cell lung cancer patients. However, no study has yet explored the regulatory role of PCat19 against NP. Our group's previous study found that PCat19 expression was consistently upregulated in a rat model of CCI. Nevertheless, the exact mechanism remains to be elucidated.

Although NP genesis is influenced by multifaceted factors, increased levels of inflammatory factors at the nerve site after affected or damaged are the main mechanism of its pathogenesis. Inflammatory reactions induce cascades that increase local perfusion volume and capillary permeability, as well as inflammatory cytokine release such as chemokines, TNF-α, and IL-6 (Sommer et al., 2018). At present, clinical research on glial cells in NP states has made obvious progress, which will have a better effect on the development of clinical treatment protocols for patients (Kong et al., 2022). Previous studies have documented crucial roles for microglia in the spinal cord in chronic pain, inflammatory pain after tissue injury, cancer pain, NP after nerve injury, and spinal cord injury (Tansley et al., 2022). Microglia in the dorsal horn of the spinal cord proliferate significantly after nerve injury and become activated, leading to an increase in their secreted pro-inflammatory factors that in turn induce and maintain NP (Inoue and Tsuda, 2018). Meanwhile, many molecules and signaling pathways (MAPK signaling pathway and nuclear factor kB) in the spinal cord are involved in microglial activation. Previous studies have found that lncRNAs are significant in mediating the activation of microglia (Tan et al., 2022). Gao et al. (2021) study suggested that lncRNA AK148321 overexpression could attenuate neuroinflammation in LPS-stimulated BV2 microglial cells. Yang et al. (2021) proposed that the upregulated lncRNA HOXA-AS2 regulates microglial polarization and in turn promotes neuroinflammation by interacting with the PRC2 complex. However, the potential function and mechanism of PCat19 in microglia mediated inflammatory response and NP remain unclear.

In this study, we first established a mouse model of chronic scientific nerve constriction injury (CCI), and then examined the changes in behavior, microglial polarization and inflammatory cytokine secretion after sciatic nerve ligation by continuous intrathecal injection of sh-PCat19. This study aimed to investigate whether PCat19 has regulatory effects on NP and the underlying mechanism. Our results provide new molecular biological information and ideas for future studies on the involvement of microglia in the development and progression of NP in vivo.