Accepted

Neuropathic pain is a major side-effect of paclitaxel (PTX) chemotherapy. Although the precise mechanisms responsible for this pain are unclear, the activation of neuroglia and upregulation of the TLR4/NF-κB pathway are known to be involved. In this study, we determined whether electroacupuncture (EA) could limit mechanical hypersensitivity resulting from the chemotherapeutic drug PTX in rats, and investigated the potential mechanisms involved.

The bladder is innervated by primary afferent nerve fibres that detect bladder distension and, via projections into the spinal cord, provide sensory input to the central nervous system circuits regulating bladder sensation and function. Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infection (UTI) in adults, inducing clinical symptoms characterised by exaggerated bladder sensation, including urgency, frequency, and pelvic pain. However, the mechanisms underlying UTI-induced modulation of bladder afferent function have yet to be explored. Here we isolated supernatants from the bladders of female mice acutely infected with UPEC (strain CFT073), or those sham-treated with phosphate buffered saline. Supernatants were then applied into the bladder lumen of healthy donor mice, and multiunit bladder afferent nerve responses to distension measured ex-vivo. Supernatant constituents from UPEC or sham-treated mice were analysed using a mouse cytokine multiplex assay. Supernatants from UPEC infected mice significantly enhanced bladder afferent firing to distension in the absence of changes in muscle compliance. Further evaluation revealed that UPEC supernatants exclusively sensitised high-threshold bladder mechanoreceptors to graded bladder distension and also recruited a population of 'silent nociceptors' to become mechanosensitive, thereby amplifying bladder afferent responses to physiological stimuli. UPEC supernatants contained significantly elevated concentrations of a range of cytokines released from innate immune cells, including, but not limited to TNFα, IL-1β, IL-6, IL-17, IFN-gamma, and MCP-1. These data provide novel mechanistic insight into how UPEC mediated UTI induces bladder hypersensitivity and the symptoms of frequency, urgency, and pelvic pain.

The present study investigated the role and molecular mechanism of long non‑coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript (MALAT)1 in neuropathic pain in rat chronic constriction injury (CCI) model. Reverse transcription‑quantitative PCR and western blot analysis were used to detect the expression levels of MALAT1, microRNA (miR)‑154‑5p and aquaporin (AQP)9 in spinal cord tissue and microglia of CCI rats. ELISA and pain behavioral assays were used to observe the effect of MALAT1 on neuropathic pain and neuroinflammation in model rats, and to verify its molecular mechanism through bioinformatics and luciferase experiments. The results of the present study identified that the expression levels of MALAT1 and AQP9 were upregulated, while miR‑154‑5p was downregulated in spinal cord tissue and microglia of CCI rats. MALAT1 knockdown in CCI model rats significantly induced the occurrence of neuropathic pain, while the upregulation of miR‑154‑5p could reverse this process. The present study also identified that miR‑154‑5p was the target gene of MALAT1, and AQP9 was the target gene of miR‑154‑5p. AQP9 knockdown promoted the occurrence of neuropathic pain. In conclusion, lncRNA MALAT1 promotes the progression of neuropathic pain in rats by reducing miR‑154‑5p and increasing AQP9. The MALAT1/miR‑154‑5p/AQP9 axis can be used as a new therapeutic target for neuropathic pain.