Back pain is common and costly. Although lumbar
disc degeneration has long been regarded as a major contributor to
back pain, how
disc degeneration leads to
back pain remains unclear. Recent studies observed microglia activation in the spinal cord after
disc degeneration, suggesting activated microglia may be involved in discogenic
back pain. To determine whether microglia activation participates in
disc degeneration-induced
back pain, we used a modified disc
puncture-induced degeneration-related
back pain mouse model to examine the changes in spinal microglia and investigate the potential link between microglia activation and discogenic
back pain. In this study, 46 CX3CR1GFP/+ male mice were used in experimental and
sham groups. A modified posterolateral retroperitoneal approach was used to expose the L3/L4 disc to induce the needle
puncture in the experimental group. Behavioral tests, including grip force and physical function, were used to measure
back pain at pre- and postsurgery. The L3 dorsal root
ganglions and lumbar spinal cord were obtained at postoperative weeks 1 to 4 followed by immunofluorescence with different
antibodies. Micrographs were obtained by confocal microscopy, and morphometric measurements of microglia were analyzed using Imaris. The punctured disc underwent progressive degeneration and mice with
disc degeneration showed impaired grip force and physical function. Compared to the control mice, the number of microglia in the lumbar spinal cord was significantly increased in the disc-punctured animals. Moreover, accumulated microglia exhibited larger
soma size and lesser ramification in the disc-injured mice. Immunofluorescence demonstrated
colony-stimulating factor 1, a
cytokine that promotes microglia repopulation, was significantly increased in L3 dorsal root
ganglions, whereas its
receptor colony-stimulating factor 1 receptor was upregulated on microglia in the disc-injured mice. In summary, lumbar disc
puncture caused progressive
disc degeneration which induced microglia activation and
back pain in mice. Increased
colony-stimulating factor 1/
colony-stimulating factor 1 receptor signaling is involved in the
disc degeneration-induced microglia activation and
back pain.