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The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling

Maiarù, M., Tochiki, K. K., Cox, M. B., Annan, L. V., Bell, C. G., Feng, X., Hausch, F. and Géranton, S. M. (2016) The stress regulator FKBP51 drives chronic pain by modulating spinal glucocorticoid signaling. Science Translational Medicine, 8 (325). 325ra19. ISSN 1946-6234

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To link to this item DOI: 10.1126/scitranslmed.aab3376

Abstract/Summary

Polymorphisms in FKBP51 are associated with stress-related psychiatric disorders and influence the severity of pain symptoms experienced after trauma. We report that FKBP51 (FK506 binding protein 51) is crucial for the full development and maintenance of long-term pain states. Indeed, FKBP51 knockout mice, as well as mice in which silencing of FKBP51 is restricted to the spinal cord, showed reduced hypersensitivity in several persistent pain models in rodents. FKBP51 deletion did not compromise the detection of acute painful stimuli, a critical protective mechanism. Moreover, the intrathecal administration of the specific FKBP51 inhibitor SAFit2 reduced the severity of an established pain state, confirming the crucial role of spinal FKBP51 in nociceptive processing. Finally, glucocorticoid signaling, which is known to modulate persistent pain states in rodents, was impaired in FKBP51 knockout mice. This finding suggested that FKBP51 regulates chronic pain by modulation of glucocorticoid signaling. Thus, FKBP51 is a central mediator of chronic pain, likely in humans as well as rodents, and is a new pharmacologically tractable target for the treatment of long-term pain states.

Item Type:Article
Refereed:Yes
Divisions:No Reading authors. Back catalogue items
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:90885
Publisher:American Association for the Advancement of Science

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