DREAM is reduced in synovial fibroblasts of patients with chronic arthritic pain: is it a suitable target for peripheral pain management?
BACKGROUND
The endogenous pain-relieving system depends in part on the regulation of nociceptive signals through binding of opioids to the corresponding opioid receptor. Interfering with the trans-repression effect of downstream regulatory element antagonist modulator (DREAM) on the transcription of the opioid dynorphin-encoding prodynorphin (pdyn) gene might enhance pain relief in the periphery.


METHODS
Expression levels were measured in osteoarthritis (OA) synovial fibroblast-like cells (SFLCs) (n = 8) and in peripheral blood mononuclear cells (PBMCs) from OA patients (n = 53) and healthy controls (n = 26) by real-time polymerase chain reaction. Lysed OA SFLCs were analyzed by immunoprecipitation. Translation of DREAM mRNA was inhibited by small interfering RNAs (siRNAs). Expressions of DREAM, pdyn, and c-fos mRNAs were measured at 24, 48, and 72 hours after transfection.


RESULTS
The expression of DREAM mRNA was shown in both healthy and OA SFLCs as well as PBMCs. Inhibiting transcription using siRNAs led to a marked reduction in DREAM expression after 24, 48, and 72 hours. However, no significant changes in c-fos and pdyn expression occurred. In addition, DREAM mRNA expression was significantly reduced in OA patients with chronic pain (pain intensity as measured by a visual analog scale scale of greater than 40), but no pdyn expression was detectable.


CONCLUSIONS
To our knowledge, this is the first report showing the expression of DREAM in SFLCs and PBMCs on the mRNA level. However, DREAM protein was not detectable. Since repression of pdyn transcription persists after inhibiting DREAM translation, DREAM appears to play no functional role in the kappa opioid receptor system in OA SFLCs. Therefore, our data suggest that DREAM appears not to qualify as a target in peripheral pain management.
Center of Experimental Rheumatology, Department of Rheumatology and Institute of Physical Medicine, University Hospital, CH-8091 Zurich, Gloriastrasse 25, Switzerland.
Natasa
N
Reisch
Andrea
A
Engler
André
A
Aeschlimann
Beat R
BR
Simmen
Beat A
BA
Michel
Renate E
RE
Gay
Steffen
S
Gay
Haiko
H
Sprott
D000328:Adult; D002478:Cells, Cultured; D002908:Chronic Disease; D019468:Disease Management; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018390:Gene Targeting / Q000639:trends; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D010146:Pain / Q000235:genetics / Q000378:metabolism*; D059408:Pain Management; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*
D051605:Kv Channel-Interacting Proteins; D012333:RNA, Messenger