Friday, April 26, 2024
4/26/2024
Abstract Widespread adoption of electric lighting has led to significant exposure to artificial light at night (LAN). Although initially assumed innocuous, exposure to LAN disrupts circadian rhythms and is correlated with increased prevalence of several clinical disorders. This so-called light pollution began prior to a deep appreciation of the importance of circadian rhythms to typical, adaptive functioning. Our preliminary data indicate that exposure to LAN disrupts circadian rhythms, dramatically increases peripheral and central inflammation, and elevates pain responsiveness in mice. Pain is a significant cause of high medical costs, lost productivity, and a common pathway to opiate addiction. Currently, there are few optimal treatments for chronic pain and the underlying causes, and predictive factors that lead individuals from therapeutic use to opiate abuse remain unspecified. Pain responsiveness shows daily variation with elevated responses at night. We hypothesize that disrupted circadian rhythms, caused by exposure to LAN, drive inflammatory processes and influence pain responsiveness. We will test this hypothesis and predict that mice exposed to dim light at night (dLAN) will display elevated pain responsiveness. We further hypothesize that circadian responses to opiate management of pain are deranged by light at night. Thus, we predict that higher doses of opiates are required to obtain similar suppression of pain responses in animals exposed to dim light at night. These hypotheses will be tested in two specific aims. In the first specific aim, we will characterize the effects of dLAN exposure on pain responsiveness in mice. Because of the well-known sex differences in pain responsiveness, we will test both male and female mice in pain responsiveness after exposure to dLAN. Circadian clocks are entrained by light interacting with melanopsin-expressing retinal ganglion cells which are primarily responsive to short-wavelength (blue) light, and relatively unresponsive to long wavelength (red) light. Thus, we will examine pain responsiveness after exposure to dark, dim white, dim blue, or dim red light at night to test the hypothesis that exposure to dLAN comprised of wavelengths that affect circadian clock entrainment (white and blue) will elevate pain responsiveness, whereas exposure to dark nights or dim red light at night prevents elevated pain responsiveness. Specific Aim 2 will test the hypothesis that disruption of circadian organization by exposure to dLAN changes sensitivity/ responsiveness to opiates. We predict that dose responses to opiates will shift so that increased opiate dosages will be required to suppress pain responses. Taken together, the results of this project will fill an important gap in knowledge about the role of circadian rhythms in pain responses and pain treatment. If our hypotheses are not disproved, then these results could easily and inexpensively be translated to individuals suffering from pain—e.g., blue-light blocking goggles or other environmental lighting adjustments—to align circadian rhythms, to improve pain treatment outcomes, and avoid opiate abuse.
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