Lumbar disc herniation may affect the spinal nerve roots through mechanical pressure, but may also induce a local inflammatory response. Therefore, in an animal model mimicking the clinical situation after intervertebral disc herniation, the spinal nociceptive signaling and the gene expression changes in nucleus pulposus (NP) and dorsal root ganglion (DRG) tissue were studied. In addition, the effect of minocycline on the spinal nociceptive signaling and on the changes in gene expression in NP tissue was investigated. Electrophysiological recordings showed that NP applied onto the dorsal nerve roots of female Lewis rats induced a significant increase in spinal nociceptive signaling. Minocycline, when applied together with NP, attenuated this increase, without having any persistent effect on nociceptive activity by itself. Furthermore, qPCR analysis of the NP tissue exposed to the dorsal nerve roots showed an increase in the gene expression of IL-1ß, Csf1 and CD68. The upregulation of IL-1ß and Csf1 suggests that NP has a pro-inflammatory effect, underlying the pro-nociceptive process after disc herniation. In addition, the upregulation of CD68 indicates phagocytic activation of NP cells following contact with the nerve roots. We also demonstrated an upregulation of FKN and its receptor CX3CR1 in NP tissue. This upregulation indicates a new mechanism for NP in the induction and/or maintenance of pain hypersensitivity. In the DRG, after NP was exposed to the dorsal nerve roots, the gene expression of TNFα, FKN and CX3CR1 was also upregulated. It is likely that this upregulation affects the excitability of primary afferent nerve fibers. This could be related to the positive feedback loop involving satellite glial cells and neurons. Minocycline inhibited the increase in gene expression of IL-1ß, Csf1, CD68, FKN and CX3CR1 in NP tissue, demonstrating an inhibitory effect on these cells, possibly through MAPK p38 inhibition. The present study suggests that disc herniation increases the excitability in nociceptive pathways, possibly through a mechanism involving both NP cells and satellite glial cells.