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.

Daniel Pitz Jacobsen,Aurora Moen,Fred Haugen,Johannes Gjerstad

doi:10.1155/2016/6519408

Daniel Pitz Jacobsen, Aurora Moen + Show 2 more

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https://doi.org/10.1155/2016/6519408

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Abstract

Introduction. Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Methods. In anaesthetized Lewis rats, extracellular single unit recordings of wide dynamic range (WDR) neurons in the dorsal horn and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3–L5). Results. A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the expression of interleukin-1β (IL-1β), colony stimulating factor 1 (Csf1), fractalkine (CX3CL1), and the fractalkine receptor CX3CR1 was increased. Minocycline, an inhibitor of microglial activation, inhibited the increase in neuronal activity and attenuated the increase in IL-1β, Csf1, CX3L1, and CX3CR1 expression in NP tissue. In addition, the results demonstrated an increase in the expression of TNF, CX3CL1, and CX3CR1 in the dorsal root ganglions (DRGs). Conclusion. Hyperexcitability in the pain pathways and the local inflammation after disc herniation may involve upregulation of CX3CL1 signaling in both the NP and the DRG.

Highlights

Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells
Earlier studies show that leakage of nucleus pulposus (NP) out of the disc after intervertebral disc herniation is associated with a local release of many substances including interleukin1β (IL-1β), tumor necrosis factor (TNF), and colony stimulating factor 1 (Csf1) [1,2,3,4]
We here report that IL-1β, TNF, Csf1, and CX3CL1, and CX3CR1 were expressed in the native NP tissue (Figure 1(a))

Summary

Introduction

Lumbar radicular pain following intervertebral disc herniation may be associated with a local inflammatory response induced by nucleus pulposus (NP) cells. Earlier studies show that leakage of nucleus pulposus (NP) out of the disc after intervertebral disc herniation is associated with a local release of many substances including interleukin1β (IL-1β), tumor necrosis factor (TNF), and colony stimulating factor 1 (Csf1) [1,2,3,4]. Such cytokines released after intervertebral disc herniation may induce increased neuronal excitability in the primary afferent nerve fibers and reduced axonal speed of conduction and may promote nerve injury [1, 5, 6]. One important inflammatory molecule possibly influencing the sensory pathways may be CX3CL1

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Conclusion