Peripheral Neuroimmune Mechanisms of Chronic Back Pain

Chronic back pain (CBP) affects 1 in 10 people worldwide, reducing mobility, productivity, and quality of life. Despite its prevalence, non-addictive treatments remain limited due to an incomplete understanding of chronic pain mechanisms. This dissertation examines peripheral neuroimmune interactions in CBP using a urokinase-type plasminogen activator (uPA)-induced mouse model (uPA-CBP). uPA, a pro-inflammatory serine protease, was injected into the L2/L3 lumbar spinous ligament, inducing prolonged mechanical and cold hypersensitivity. Flow cytometry of dorsal root ganglia (DRG) showed increased CD45+CD11b+ myeloid cells in males and CD45+CD3+CD4+ lymphocytes in females. DRG neurons from male uPA-CBP mice exhibited heightened action potential firing. Pharmacological inhibition of colony-stimulating factor 1 receptor (CSF1R) via PLX5622 reduced pain behavior and nociceptor hyperexcitability. RNA sequencing identified upregulation of genes linked to leukocyte migration, inflammation, and ion channel modulation, supporting DRG neuroimmune involvement in CBP. These findings establish uPA-CBP as a valuable model for advancing pain management strategies.