New analysis led by investigators at Massachusetts General Hospital (MGH) gives insights on why individuals with crimson hair exhibit altered sensitivity to sure sorts of pain. The findings are printed in Science Advances.
In individuals with crimson hair (as in quite a few different species of animals with crimson fur), the pigment-producing cells of the pores and skin — referred to as melanocytes — include a variant type of the melanocortin 1 receptor. This receptor sits on the cell floor, and if it turns into activated by circulating hormones referred to as melanocortins, it causes the melanocyte to modify from producing yellow/crimson melanin pigment to producing brown/black melanin pigment. Earlier work by David E. Fisher, MD, PhD, director of the Mass General Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center, demonstrated that the lack of red-haired people to tan or darken their pores and skin pigment is traced to inactive variants of this receptor.
To examine the mechanisms behind different pain thresholds in red-haired people, Fisher and his colleagues studied a pressure of red-haired mice that (as in people) incorporates a variant that lacks melanocortin 1 receptor operate and additionally reveals larger pain thresholds.
The crew discovered that lack of melanocortin 1 receptor operate in the red-haired mice brought about the animals’ melanocytes to secrete decrease ranges of a molecule referred to as POMC (proopiomelanocortin) that’s subsequently reduce into different hormones together with one which sensitizes to pain and one which blocks pain. The presence of those hormones maintains a stability between opioid receptors that inhibit pain and melanocortin 4 receptors that improve notion of pain.
In red-haired mice (and subsequently, probably people), having each hormones at low ranges would seemingly cancel one another out. However, the physique additionally produces extra, non-melanocyte-related components that activate opioid receptors involved in blocking pain. Therefore, the web impact of decrease ranges of the melanocyte-related hormones is extra opioid indicators, which elevates the brink for pain.
“These findings describe the mechanistic basis behind earlier evidence suggesting varied pain thresholds in different pigmentation backgrounds,” says Fisher. “Understanding this mechanism provides validation of this earlier evidence and a valuable recognition for medical personnel when caring for patients whose pain sensitivities may vary.”
Fisher provides that the outcomes recommend new methods to control the physique’s pure processes that management pain notion — for instance, by designing new drugs that inhibit melanocortin 4 receptors involved in sensing pain.
“Our ongoing work is focused on elucidating how additional skin-derived signals regulate pain and opioid signaling,” provides co-lead writer Lajos V. Kemény, MD, PhD, a analysis fellow in Dermatology at MGH. “Understanding these pathways in depth may lead to the identification of novel pain-modulating strategies.”
This work was supported by the National Institutes of Health, the Melanoma Research Alliance, the U.S.-Israel Binational Science Foundation, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.
Materials offered by Massachusetts General Hospital. Note: Content may be edited for type and size.