Local Application of Nucleus Pulposus Induces Expression of P2x3 in Rat Dorsal Root Ganglion Cells

Abstract

: The P2X 3 receptor is a ligand -gated cation channel that is activated by extra cellular adenosine triphosphate (ATP) found in the dorsal root, trigeminal and nodose ganglia. It is one of the receptors transmitting nociceptive information of injuries and inflammation of the periphery by endogenous ATP released from damaged cells. The present study was performed in order to evaluate if there was an increased expression of P2X 3 -immunoreactivity in dorsal root ganglion (DRG) neurons after experimental disc herniation. There were four groups : exposure of the left L4 dorsal root ganglion and incision of the L4 -L5 disc, exposure and slight displacement of the left L4 dorsal ganglion, sham exposure of the L4 dorsal root ganglion, and normal. Seven days after surgery, the DRG's were collected, sectioned and stained immunohistochemically for the P2X 3 receptor. The expression of P2X 3 increased significantly following incision of the L4 -5 disc compared to the normal group. Sham surgery induced a minor, although statistically significant increase. Mechanical displacement did not induce any increased expression of the receptors. The study demonstrates that expression of the P2X 3 receptors in the DRG may be induced by local application of nucleus pulposus. This may increase our understanding of the pathophysiologic mechanisms related to disc herniation and sciatica.

Hyperexcitability in Spinal WDR Neurons following Experimental Disc Herniation Is Associated with Upregulation of Fractalkine and Its Receptor in Nucleus Pulposus and the Dorsal Root Ganglion

“…Still, a significant increase in the expression of TNF, CX3CL1, and CX3CR1 was demonstrated, supporting the previous observation that local application of NP onto the primary afferents may change the gene expression in the DRGs [37]. The changes in gene expression were only observed on the ipsilateral side.…”

Sensitization of P2Χ3 Receptors by Cystathionine β-Synthetase Mediates Persistent Pain Hypersensitivity in a Rat Model of Lumbar Disc Herniation

“…Recent reports have shown an increase in P2X3R expression in primary sensory afferents [19,20]. In addition, local application of nucleus pulposus induces expression of P2X3Rs in rat dorsal root ganglion cells [9], suggesting a role for P2X3Rs in disc herniation and sciatica. However, the mechanism underlying P2X3R upregulation under LDH conditions remains largely unknown.…”

“…Inflammatory reactions between nucleus pulposus (NP) and the nerve roots have been suggested to play an important role in disc herniation with sciatica [1][2][3][4][5]. Experimental studies have demonstrated that epidural application of NP leads to pronounced morphologic and functional changes in the nerve roots [6][7][8][9]. However, the pathogenic mechanisms linking herniated NP, gene expression, and pain hypersensitivity are not well understood.…”