IL-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain

Pain, 2018 · DOI: 10.1097/j.pain.0000000000001109 · Published: March 1, 2018

Immunology Pain Management Rehabilitation

Simple Explanation

This study investigates how low-intensity exercise reduces neuropathic pain in mice. It focuses on the role of the immune system and specific molecules called cytokines. The research shows that exercise increases anti-inflammatory cytokines like IL-4 at the site of nerve injury and in the spinal cord, which helps reduce pain. Mice lacking IL-4 did not experience pain relief from exercise. Exercise also changes the type of immune cells (macrophages) present at the injury site, promoting those that reduce inflammation. These changes suggest exercise can alter the neuroimmune system to alleviate neuropathic pain.

Study Duration

2 weeks

Participants

Swiss, Balb/cJ, and IL-4−/− mice

Evidence Level

Not specified

Key Findings

1
Low-intensity treadmill exercise improved neuropathic pain behaviors in mice, including mechanical hyperalgesia, escape/avoidance behavior, and spontaneous locomotor activity.
2
Exercise increased the levels of anti-inflammatory cytokines (IL-4, IL-1ra, IL-5) in the sciatic nerve and spinal cord of mice with peripheral nerve injury.
3
Mice lacking IL-4 (IL-4−/−) or treated with an IL-4 antibody did not develop analgesia to treadmill exercise, indicating that IL-4 is crucial for exercise-induced pain relief.

Research Summary

This study investigates the mechanisms by which low-intensity exercise reduces neuropathic pain in mice after peripheral nerve injury (PNI). The researchers hypothesized that exercise restores anti-inflammatory cytokines at the injury site and in the spinal cord. The study found that exercise improves pain behaviors, increases anti-inflammatory cytokines (IL-4, IL-1ra, IL-5), and alters macrophage phenotype at the injury site, promoting M2 macrophages (anti-inflammatory). The findings suggest that IL-4 plays a key role in exercise-induced analgesia by modulating neuroimmune responses in both the peripheral and central nervous systems.

Practical Implications

Therapeutic Target

IL-4 can be a therapeutic target for managing neuropathic pain.

Exercise Prescription

These studies will provide a rationale for both clinicians and patients to prescribe and adhere to an exercise program.

Neuroimmune Modulation

Low-intensity exercise positively modulates the state of the immune system at multiple sites to favor anti-inflammatory cytokines over pro-inflammatory cytokines increases to prevent development of neuropathic pain.