Blockade of IgG Fc receptors reduces pain after intervertebral disc injury

Intervertebral disc (IVD) injury is a common cause of low back pain and disability. Recent evidence suggests that autoantibodies contribute to such pain. We, therefore, explored the hypothesis that a novel IgG Fc receptor blocker could reverse chronic pain-related behaviors in a mouse model of IVD injury.

These studies used a multi-level lumbar IVD puncture model of low back pain in male C57BL/6 mice. Additional mouse strains evaluated included Fc gamma chain knockouts failing to express excitatory IgG Fc receptors and muMT mice incapable of producing mature B lymphocytes or antigen-specific IgG. Nociceptive testing consisted of hindpaw mechanical allodynia and pinch hyperalgesia. The expression of FcgrI and FcgrIII excitatory IgG Fc receptors and FcgrIIb inhibitory receptors was measured in lumbar sensory ganglia and spinal cord tissue using qPCR. The accumulation of IgG was measured using immunoblotting.

After disc injury, wild-type mice developed chronic hindpaw mechanical allodynia and pinch hyperalgesia. At 10 weeks post-injury, FcgrI, FcgrIIb and FcgrIII receptor expression were all increased in lumbar sensory ganglia and lumbar spinal cord tissue. Disc injury also caused IgG deposition at 10 weeks in the injured tissues and corresponding spinal cord. Treating disc-injured mice with the pan IgG Fc receptor interacting molecule (PRIM) reversed pain behaviors.

Injury of mouse IVDs leads to persistent nociceptive sensitization in mice which can be reduced by administration of PRIM. Blockade of IgG Fc receptors may be a viable approach to the treatment of low back pain.