Reduced MC4R signaling alters nociceptive thresholds associated with red hair, 2021, Robinson et al

Reduced MC4R signaling alters nociceptive thresholds associated with red hair

Kathleen C. Robinson, Lajos V. Kemény, Gillian L. Fell, Andrea L. Hermann, Jennifer Allouche , Weihua Ding, Ajay Yekkirala, Jennifer J. Hsiao, Mack Y. Su, Nicholas Theodosakis , Gabor Kozak , Yuichi Takeuchi, Shiqian Shen, Antal Berenyi , Jianren Mao, Clifford J. Woolf , David E. Fisher

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 proopiomelanocortin transcription and systemic melanocyte-stimulating hormone (MSH) levels in the plasma of red-haired (Mc1re/e) mice. Decreased peripheral α-MSH derepresses the central opioid tone mediated by the opioid receptor OPRM1, resulting in increased nociceptive thresholds. We identified MC4R as the MSH-responsive receptor that opposes OPRM1 signaling and the periaqueductal gray area in the brainstem as a central area of opioid/melanocortin antagonism. This work highlights the physiologic role of melanocytic MC1R and circulating melanocortins in the regulation of nociception and provides a mechanistic framework for altered opioid signaling and pain sensitivity in red-haired individuals.

Open: https://www.science.org/doi/full/10.1126/sciadv.abd1310

 

Of interest because it demonstrates the potential for small genetic variation to have subtle impacts on function.

 

Also of interest because the abstract’s first line implies that some red-haired mice are not naturally red-haired. The vain little monsters must go on daring nocturnal missions to steal hair dye.

 

Henna'ed mice!


ETA: I now have visions of them wrapped in tinfoil, like a woman I house-shared with in the 70s.

 

At least they will be safe from 5G mast covid rays.