Increased C-fiber response induced by experimental disc herniation is associated with upregulation of fractalkine and its receptor in nucleus pulposus and dorsal root ganglion

Abstract

Abstract Aims Lumbar radicular pain following intervertebral disc herniation may be caused by a local inflammatory response induced by nucleus pulposus (NP) cells. Here in an animal model mimicking the clinical situation following disc herniation we investigated the effect of NP on the spinal nociceptive signaling and local gene expression. Methods In anaesthetized Lewis rats, extracellular single unit recordings of spinal nociceptive activity and qPCR were used to explore the effect of NP application onto the dorsal nerve roots (L3-L5). All animal experiments were approved by the Norwegian Animal Research Authority and were performed in conformity with the laws and regulations controlling experiments and procedures on live animals in Norway. Results A clear increase in C-fiber response was observed following NP conditioning. In the NP tissue, the gene expression of interleuking-1 β (IL-1β), colony stimulating factor 1 (Csf1), fractakine (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 gene expression in NP tissue. Interestingly, gene expression analysis demonstrated an increase in the expression of TNF, CX3CL1 and CX3CR1 in the dorsal roots ganglion (DRG). An increase in the expression of IL-1 β and TNF in cultured DRG cells was also induced in vitro. Conclusions The present study suggests that hyperexcitability in the pain pathways after disc herniation may involve upregulation of CX3CL1 signaling in NP - but also in the DRG.