Normalizing JMJD6 Expression in Rat Spinal Dorsal Horn Alleviates Hyperalgesia Following Chronic Constriction Injury

Abstract

Jumonji domain-containing protein 6 (JMJD6) is a homolog of hypoxia-inducible factor (HIF) asparaginyl hydroxylase, an inhibitor of HIF. HIF-1α is known to participate in neuropathic pain (NPP) during chronic constriction injury (CCI); however, the roles of JMJD6 in NPP have not been systematically investigated. In this study, we examined the temporal distribution and cellular location of JMJD6 in the spinal cord during CCI. In addition, we assessed behavioral changes representative of NPP in rats. Following CCI, lentiviral vectors (LV-JMJD6) were intrathecally administered to observe the changes in the expression of JMJD6, HIF-1α, and its downstream factor caspase-3. Co-immunoprecipitation was used to detect potential interactions between JMJD6 and HIF-1α. We found that JMJD6 was decreased in rats following CCI, which was accompanied by significant NPP–associated behavioral changes. JMJD6 was mainly expressed in neurons. Intrathecal injection of LV-JMJD6 following CCI alleviated the thermal and mechanical hyperalgesia, normalized JMJD6 protein expression, and decreased HIF-1α protein expression with a corresponding reduction in caspase-3 protein expression. Furthermore, the co-immunoprecipitation analyses showed that JMJD6 and HIF-1α protein immunoprecipitated with each other, indicating an interaction between these two proteins. Taken together, the results suggest that JMJD6 may serve as a sensor in neurons of the adult rat spinal cord during the CCI state. Furthermore, JMJD6 may exert its function in NPP by regulating HIF-1α in rats exposed to CCI.

Normalizing HDAC2 Levels in the Spinal Cord Alleviates Thermal and Mechanical Hyperalgesia After Peripheral Nerve Injury and Promotes GAD65 and KCC2 Expression

“…TSA was injected for 3 consecutive days with the first injection on the seventh day after CCI surgery to ensure establishment of neuropathic pain. A 10 μL intrathecal injection was administered as reported previously under isoflurane anesthesia (Mo et al, 2018). Sham-operated rats and DMSO-treated rats received 5% DMSO, and TSA-treated rats received TSA doses of either 2 or 10 μg (one dose per day).…”

Silencing of lncRNA PKIA-AS1 Attenuates Spinal Nerve Ligation-Induced Neuropathic Pain Through Epigenetic Downregulation of CDK6 Expression

“…Peripheral inflammation and nerve injury can alter the expression of numerous genes, including lncRNAs, in affected pain pathways (Jiang et al, 2015; Wu et al, 2018). Moreover, numerous lncRNAs have been identified in the pain-related regions, such as dorsal root ganglion and spinal cord of mouse, rat, and human (Hu et al, 2016; Dou et al, 2017; Mo et al, 2018). The spinal cord dorsal horn is responsible for relaying and modulating pain-related signals from nociceptors to the supraspinal brain regions.…”

17β-Estradiol Attenuates Neuropathic Pain Caused by Spared Nerve Injury by Upregulating CIC-3 in the Dorsal Root Ganglion of Ovariectomized Rats

“…Neuropathic pain is a worldwide health concern with poor treatment outcomes (Norcini et al, 2016; Mo et al, 2018; Ouyang et al, 2019). Increases in spontaneous ectopic discharge in DRG neurons have been shown to play a critical role in neuropathic pain genesis (Mo et al, 2018). Small and medium-sized DRG cells were used for all patch clamp experiments.…”