Distinct Gene Expression Patterns of Ion Channels and Cytokines in Rat Primary Sensory Neurons During Development of Bone Cancer and Cancer Pain

Abstract

Cancer and cancer pain processes a major clinical challenge and the underlined mechanisms of pathogenesis remain elusive. We examined the specific changes in the transcriptomic profiles in the dorsal root ganglion (DRG) neurons of rats with bone cancer and bone cancer pain (BCP) using RNA sequencing technology. The bone cancer and BCP was induced by tumor cells implantation (TCI) into the tibia bone cavity in adult female rats. One week after treatment, TCI caused up- and down-regulation of thousands of genes in DRG. These genes were mainly involved in the immune process, inflammatory response, and intracellular signaling transduction of carbohydrate and cytokine. The cAMP and calcium signaling pathways were the major processes in the initial responses. Differentially expressed gene (DEG) analysis further showed that the genes for ion channels increased during day 1-7, while the genes for cytokine signaling pathways sustainedly increased during day 7-14 after TCI. The time courses of gene expression for ion channels and cytokines support their distinct roles in the early induction and late maintenance of BCP development. In addition, among the top 500 up- and down-regulated genes, 80-90% were unique for bone cancer pain as well as neuropathic and inflammatory pain, while less than 2% were shared among the three different forms of pain. This study reveals the uniqueness of mechanisms underlying bone cancer with pain, which is, to a large extent, differently from pain after acute inflammatory and nerve injury and provides novel potential targets of DEGs for bone cancer with pain.

Transcriptome Sequencing Explores the Mechanism of Baicalin on Bone Cancer Pain

“…It has been reported that the development of bone cancer pain was accompanied by the expression of many genes in peripheral and central nervous system were changed. [16][17][18][19] Some researchers also found the changes of bone cancer pain gene expression profile by transcriptome sequencing. Some genes for the progression of pain hypersensitivity have also been discovered.…”

Diclofenac Sodium Nanomedicine Results in Pain-relief and Differential Expression of the RNA Transcriptome in the Spinal Cord of Spared Nerve Injury Rats

“…The resulting data were quality-controlled and analyzed using bioinformatics methods. The rest samples were stored at -80°C [44][45][46].…”

Acquisition and validation of four painful subtypes of colon adenocarcinoma and prognostic analysis

“…The incidence of chronic pain after surgical cancer treatment varies signi cantly with the type of cancer, treatment method, age, inherited variability, and psychiatric factors [21] . Oncogenes have now been found to be associated with the development of cancer with pain [22] . The ndings on pain-related genes in cancer patients can provide a reference for the development of the target drugs for tumor therapy, which is of great signi cance for alleviating pain and improving the quality of life of cancer patients [23] .…”