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2014 ; 157
(7
): 1527-34
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Skin ?-endorphin mediates addiction to UV light
#MMPMID24949966
Fell GL
; Robinson KC
; Mao J
; Woolf CJ
; Fisher DE
Cell
2014[Jun]; 157
(7
): 1527-34
PMID24949966
show ga
UV light is an established carcinogen, yet evidence suggests that UV-seeking
behavior has addictive features. Following UV exposure, epidermal keratinocytes
synthesize proopiomelanocortin (POMC) that is processed to melanocyte-stimulating
hormone, inducing tanning. We show that, in rodents, another POMC-derived
peptide, ?-endorphin, is coordinately synthesized in skin, elevating plasma
levels after low-dose UV. Increases in pain-related thresholds are observed and
reversed by pharmacologic opioid antagonism. Opioid blockade also elicits
withdrawal signs after chronic UV exposure. This effect was sufficient to guide
operant behavioral choices to avoidance of opioid withdrawal (conditioned place
aversion). These UV-induced nociceptive and behavioral effects were absent in
?-endorphin knockout mice and in mice lacking p53-mediated POMC induction in
epidermal keratinocytes. Although primordial UV addiction, mediated by the
hedonic action of ?-endorphin and anhedonic effects of withdrawal, may
theoretically have enhanced evolutionary vitamin D biosynthesis, it now may
contribute to the relentless rise in skin cancer incidence in humans.
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