302 Increased nociceptive thresholds associated with red hair are caused by reduced MC4R signaling

Abstract

Humans and mice with natural red hair have elevated basal pain thresholds and an increased sensitivity to opioid analgesics. We investigated the mechanisms responsible for higher nociceptive thresholds in red-haired mice resulting from a loss of melanocortin 1 receptor (MC1R) function and found that the increased thresholds are melanocyte-dependent but melanin-independent. MC1R loss of function decreases melanocytic pro-opiomelanocortin transcription and systemic melanocyte stimulating hormone (MSH) levels in the plasma of red-haired (Mc1re/e) mice.