Earlier onset of chemotherapy-induced neuropathic pain in females by ICAM-1-mediated accumulation of perivascular macrophages.

Summary

Using clinical data and mechanistic mouse experiments, the authors show that bortezomib-associated neuropathic pain manifests earlier in females via ICAM-1–driven perivascular monocyte/macrophage accumulation in the spinal cord and CCL1-mediated neuronal activation. This sex-specific pathway provides actionable targets for prevention or early intervention in female patients.

Key Findings

• Peripheral sensory disorders occurred earlier in female patients than in males after bortezomib treatment.
• BTZ elevated ICAM-1 and promoted perivascular monocyte/macrophage infiltration in female mouse spinal cord.
• Macrophage-derived CCL1 directly and indirectly (via astrocytes) activated neurons, accelerating neuropathic pain onset in females.

Clinical Implications

For anesthesiologists and pain specialists, peri-chemotherapy strategies could incorporate ICAM-1/CCL1 pathway modulation or macrophage trafficking blockade to prevent early neuropathic pain in women receiving bortezomib. Risk stratification and sex-specific monitoring protocols may reduce chronic pain burden.

Limitations

• Clinical component is retrospective and limited to bortezomib-treated populations; causality in humans not proven.
• Translational gap remains regarding pharmacologic targeting of ICAM-1/CCL1 in patients.

Future Directions

Prospective human studies stratified by sex to validate biomarkers (ICAM-1, CCL1) and trials of macrophage trafficking or CCL1 antagonism to prevent chemotherapy neuropathy in women.