REVISTA

Influencia del ciclo circadiano en la liberación de glucocorticoides sobre el dolor

Valoración Valoración: 4 Estrellas

Descripción: La liberación diurna de glucocorticoides podría influir en los procesos de alodinia mecánica en los astrocitos espinales.

TITULO FUENTE ORIGINAL:

Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia.

AUTORES:

Koyanagi S, Kusunose N, Taniguchi M, Akamine T, Kanado Y, Ozono Y, Masuda T, Kohro Y, Matsunaga N, Tsuda M, Salter MW, Inoue K, Ohdo S

REVISTA ABREV.:

Nat Commun

AÑO:

2016

REFERENCIA:

7:13102

DOI:

10.1038/ncomms13102

RESUMEN ORIGINAL:

Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated... + Leer más

Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn. We identify serum- and glucocorticoid-inducible kinase-1 (SGK-1) as the key molecule responsible for the glucocorticoid-enhanced release of ATP from astrocytes. SGK-1 protein levels in spinal astrocytes are increased in response to glucocorticoid stimuli and enhanced ATP release by opening the pannexin-1 hemichannels. Our findings reveal an unappreciated circadian machinery affecting pain hypersensitivity caused by peripheral nerve injury, thus opening up novel approaches to the management of chronic pain.

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