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bibliography * The PainScience Bibliography contains plain language summaries of thousands of scientific papers and others sources, like a specialized blog. This page is about a single scientific paper in the bibliography, Hand 2016.

Suppression of inflammation at night might explain morning stiffness

Hand LE, Hopwood TW, Dickson SH, Walker AL, Loudon AS, Ray DW, Bechtold DA, Gibbs JE. The circadian clock regulates inflammatory arthritis. FASEB J. 2016 Aug. PubMed #27488122.
Tags: inflam-sys, aging, arthritis, neat, biology, pain problems

PainSci summary of Hand 2016?This page is one of thousands in the bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided at the bottom of the page, as often as possible. ★★★☆☆?3-star ratings are for typical studies with no more (or less) than the usual common problems. Ratings are a highly subjective opinion, and subject to revision at any time. If you think this paper has been incorrectly rated, please let me know.

This research describes a protein, cryptochrome, which may be used by the body’s biological clock to suppress inflammation during the night — which may be why we are so often sore and stiff in the morning when the suppression wears off. More broadly, this mechanism strongly suggests that inflammation varies in daily rhythms controlled by the brain.

“The clinical implications are far-reaching,” said Thoru Pederson, PhD, Editor-in-Chief of The FASEB Journal. The main one, of course, is the tantalizing possibility that cryptochrome could be used as an anti-inflammatory at other times of day.

This nightly suppression may not occur in everyone or with all kinds of inflammation. This was a test tube study, looking at the effects of depriving harvested cells of cryptochrome, and then re-supplying it. It acted like an anti-inflammatory in that relatively simple context, but human physiology is always more complicated.

Nevertheless, it’s intriguing. Widespread inflammation has many pathological causes, but it’s also just part of aging. “Human aging is characterized by a chronic, low-grade inflammation,” (Franceschi 2014) known as “inflammaging.” The contrast between normal levels inflammation and the suppressed levels at night may get greater as we age.

~ Paul Ingraham

original abstract

There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases. To investigate mechanistic links between the biological clock and pathways underlying inflammatory arthritis, mice were administered collagen (or saline as a control) to induce arthritis. The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression. Inflammatory markers were significantly repressed during the dark phase. Further work demonstrated an active molecular clock within the inflamed limbs and highlighted the resident inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of the rhythmic inflammatory signal. Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation. Finally, the results show that the core clock proteins CRYPTOCHROMES 1 and 2 repressed inflammation within the FLSs, and provide novel evidence that a CRYPTOCHROME activator has anti-inflammatory properties in human cells. We conclude that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.-Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I., Ray D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates inflammatory arthritis.

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