| First Author | Guo Y | Year | 2017 |
| Journal | Neuropharmacology | Volume | 117 |
| Pages | 292-304 | PubMed ID | 28232180 |
| Mgi Jnum | J:336467 | Mgi Id | MGI:6834340 |
| Doi | 10.1016/j.neuropharm.2017.02.019 | Citation | Guo Y, et al. (2017) Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons. Neuropharmacology 117:292-304 |
| abstractText | Painful nerve injury disrupts Ca(2+) signaling in primary sensory neurons by elevating plasma membrane Ca(2+)-ATPase (PMCA) function and depressing sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) function, which decreases endoplasmic reticulum (ER) Ca(2+) stores and stimulates store-operated Ca(2+) entry (SOCE). The extracellular matrix glycoprotein thrombospondin-4 (TSP4), which is increased after painful nerve injury, decreases Ca(2+) current (ICa) through high-voltage-activated Ca(2+) channels and increases ICa through low-voltage-activated Ca(2+) channels in dorsal root ganglion neurons, which are events similar to the effect of nerve injury. We therefore examined whether TSP4 plays a critical role in injury-induced disruption of intracellular Ca(2+) signaling. We found that TSP4 increases PMCA activity, inhibits SERCA, depletes ER Ca(2+) stores, and enhances store-operated Ca(2+) influx. Injury-induced changes of SERCA and PMCA function are attenuated in TSP4 knock-out mice. Effects of TSP4 on intracellular Ca(2+) signaling are attenuated in voltage-gated Ca(2+) channel alpha2delta1 subunit (Cavalpha2delta1) conditional knock-out mice and are also Protein Kinase C (PKC) signaling dependent. These findings suggest that TSP4 elevation may contribute to the pathogenesis of chronic pain following nerve injury by disrupting intracellular Ca(2+) signaling via interacting with the Cavalpha2delta1 and the subsequent PKC signaling pathway. Controlling TSP4 mediated intracellular Ca(2+) signaling in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain. |
