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Study Identifies Immune Off Switch Behind Why Pain Lasts Longer in Women

Testosterone-driven IL-10 monocytes appear to speed pain resolution in males.

These side-by-side microscope images demonstrate lower IL-10 receptor subunit levels, shown in yellow, in female skin cells (left) than in male cells (right).
Testosterone-activated monocytes in males produce higher levels of IL-10 (shown in yellow), which signals neurons to resolve pain more rapidly than in females. Credit: Neuroscience News
She holds her head in her hands and slumps down. Headache. She is troubled. Mental pain, suffering, grief. Loneliness, alienation. Instability. Depression. Trauma. She is a Japanese woman in her seventies.
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Overview

  • Peer-reviewed research in Science Immunology pinpoints monocyte-derived IL-10 as an active mechanism that resolves pain and is more robust in males.
  • In mice, deleting Il10 in monocytes or the Il10 receptor in sensory neurons impeded recovery, demonstrating causality in the IL-10 pathway.
  • A human cohort of about 245 trauma patients showed men’s pain subsided faster and correlated with higher circulating IL-10 and more IL-10–producing monocytes.
  • Androgen signaling increased IL-10 production: blocking male hormones removed the male advantage, while testosterone given to female mice boosted IL-10+ monocytes and accelerated recovery.
  • Enhancing IL-10+ monocytes with resolvin D1 eliminated sex differences in mice, suggesting non-opioid targets, though experts caution human therapies remain unproven and may not explain all chronic pain conditions.