Mechanism of Incisional Pain: Novel Finding on Long Noncoding RNA XIST/miR-340-5p/RAB1A Axis

The objective of this study is to investigate the effect of long noncoding RNA (lncRNA) XIST on postoperative pain and inflammation of plantar incision pain (PIP) in rats and its underlying mechanisms. PIP rat models were established by plantar incision. Rats in the sham group were subjected to povidone-iodine scrubbing, and no incision was made. To explore the role of XIST/miR-340-5p/RAB1A in postoperative pain and inflammation, PIP rats were separately or simultaneously injected with lentivirus containing sh-NC, sh-XIST, mimic NC, miR-340-5p mimic, inhibitor NC, miR-340-5p inhibitor, pcDNA3.1, or pcDNA3.1-RAB1A through an intrathecal catheter. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values of rats in each group were assessed to evaluate the pain behavior. RT-qPCR and Western blot were utilized to determine the levels of XIST, miR-340-5p, RAB1A, and NF-κB pathway-related proteins (p-IκBα, IκBα, p-p65, and p65). The concentrations of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in rat spinal dorsal horn tissues were inspected by ELISA. H and E staining was applied to observe the pathological changes of neurons in the spinal dorsal horn, TUNEL staining to detect neuronal apoptosis, and immunohistochemistry to measure RAB1A level. Plantar incision surgery caused decreased PWT and PWL values, enhanced levels of XIST, RAB1A, and inflammatory cytokines, along with an increased proportion of apoptotic neurons. The pain sensitivity and inflammation of rats were motivated after plantar incision surgery. Intrathecal injection of sh-XIST or miR-340-5p mimic ameliorated the pain and inflammation of PIP rats, while silencing of miR-340-5p or overexpression of RAB1A partly reversed the effect of sh-XIST on PIP rats. XIST targeted miR-340-5p and miR-340-5p negatively regulated RAB1A. The XIST/miR-340-5p/RAB1A axis activated the NF-κB signaling pathway. LncRNA XIST aggravates inflammatory response and postoperative pain of PIP rats by activating the NF-κB pathway via the miR-340-5p/RAB1A axis.