Reduced MC4R signaling alters nociceptive thresholds associated with red hair.
Sci Adv
; 7(14)2021 04.
Article
en En
| MEDLINE
| ID: mdl-33811065
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Nocicepción
/
Analgésicos Opioides
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article