Pronociceptive autoantibodies in the spinal cord mediate nociceptive sensitization, loss of function, and spontaneous pain in the lumbar disc puncture model of chronic back pain

Pain, 2023 · DOI: 10.1097/j.pain.0000000000002725 · Published: February 1, 2023

Immunology Pain Management Musculoskeletal Medicine

Simple Explanation

This study investigates the role of the immune system, specifically B cells and autoantibodies, in chronic low back pain using a mouse model. Mice with a disc puncture developed long-lasting pain and functional deficits. The study found that mice lacking B cells and antibodies experienced less pain and functional impairment after disc puncture, suggesting a role for these immune components in pain development. The researchers also identified that specific autoantibodies, particularly IgM, play a key role in sensitizing pain pathways in the spinal cord, leading to chronic pain behaviors.

Study Duration

24 weeks

Participants

3 months old male and female muMT mice lacking mature B cells and immunoglobulin, with wildtype C57BL/6J controls

Evidence Level

Not specified

Key Findings

1
Lumbar disc puncture in mice induces chronic hindpaw mechanical allodynia, hyperalgesia, grip weakness, and spontaneous pain, lasting up to 24 weeks.
2
Mice lacking B cells and antibodies (muMT mice) showed attenuated or absent pain responses after disc puncture, indicating a role for adaptive immunity.
3
Intrathecal injection of IgM antibodies from disc puncture mice into muMT mice caused nociceptive sensitization, highlighting the pronociceptive role of these autoantibodies.

Research Summary

This study investigated the role of pronociceptive autoimmune responses in the spinal cord in mediating pain behaviors, functional loss, and spontaneous pain in a lumbar disc puncture model of low back pain in mice. The researchers found that lumbar disc injury leads to long-lasting pain and functional deficits, and that mice lacking B cells and antibodies failed to develop the full pain-related phenotypic changes observed in wildtype mice after disc injury. The study also identified that intrathecal injection of disc puncture mouse IgM, but not IgG, was pronociceptive in muMT disc puncture mice, and lumbar disc injury induced IgM deposition in lumbar discs and spinal cord.

Practical Implications

Therapeutic targets

Identifies B cells and IgM autoantibodies as potential therapeutic targets for chronic low back pain.

Personalized medicine

Suggests that understanding individual autoimmune profiles could lead to more targeted and effective pain management strategies.

Preclinical model

Establishes a murine model for studying pronociceptive autoimmune responses in low back pain.

Study Limitations

1
The study used a mouse model, which may not fully replicate the complexities of human low back pain.
2
The exact neoantigens targeted by the autoantibodies were not fully identified.
3
The study focused on the role of B cells and autoantibodies, but other immune cells and factors may also contribute to chronic pain.

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