Chronic stress-induced changes in pro-inflammatory cytokines and spinal glia markers in the rat: a time course study.
OBJECTIVE
Spinal glia activation has been proposed as one mechanism underlying visceral hyperalgesia in a rodent model of chronic stress. In order to assess the possible role of changes in circulating cytokines and in blood-spinal cord barrier (BSCB) permeability in spinal glia activation, we studied the time course of peripheral and spinal pro-inflammatory cytokines and of spinal and satellite glia markers in response to repeated water avoidance (WA) stress.


METHODS
Spinal cords and dorsal root ganglion cells (DRGs) were collected from control rats, rats exposed to 1-hour WA, or 1-hour WA daily for 5 days or 1-hour WA daily for 10 days.


RESULTS
We demonstrated a time-dependent change in circulating IL-1β and spinal IL-1β, IL-6 and TNF-α in stressed animals compared with controls. We found altered expression of the astrocyte markers GFAP and Connexin 43 in spinal and DRG samples at different time points. Finally, WA was associated with increased BSCB permeability.


CONCLUSIONS
These findings confirm the concept that both peripheral and spinal immune markers are altered after chronic WA and suggest a possible link between stress-induced increase of peripheral pro-inflammatory cytokines, changes in satellite glial cells, increase in BSCB permeability and increase in spinal pro-inflammatory mediators suggesting glia activation.
Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, UCLA David Geffen School of Medicine, Los Angeles, CA 90095-7378, USA.
Viktoriya
V
Golovatscka
Helena
H
Ennes
Emeran A
EA
Mayer
Sylvie
S
Bradesi
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009457:Neuroglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism*; D013315:Stress, Psychological / Q000276:immunology* / Q000523:psychology
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators