Selective contribution of Egr1 (zif/268) to persistent inflammatory pain.
The zinc finger transcription factor Egr1 is critical for coupling extracellular signals to changes in cellular gene expression. Expression of Egr1, as well as other immediate early genes, is up-regulated in response to a number of noxious stimuli. Activity-dependent activation of Egr1 has been reported in forebrain regions, including the anterior cingulate cortex (ACC), after peripheral injury. However, no study has reported a direct contribution of Egr1 to behavioral nociceptive responses. Here, we use Egr1 knockout mice to show that Egr1 is selectively required for behavioral responses to persistent inflammatory pain. Behavioral responses to peripheral inflammation were significantly reduced in Egr1 knockout mice, whereas responses to acute noxious stimuli were normal. In addition, inflammation triggered an up-regulation of Egr1 expression in the ACC of wild-type mice. Last, synaptic potentiation induced by theta (theta) burst stimulation in the ACC was significantly reduced or blocked in Egr1 knockout mice. Our study suggests that the transcription factor Egr1 plays a selective role in nociceptive behavioral responses to persistent inflammatory pain but not to acute noxious stimuli.


CONCLUSIONS
Chronic pain diminishes the quality of life. Here, we show that the immediate early gene Egr1 plays a role in chronic inflammatory, but not acute, pain. Egr1 knockout mice showed reduced nociceptive behaviors to persistent inflammatory pain and inflammation increased Egr1 expression in the anterior cingulate cortex of wild-type mice.
Ko
Shanelle W
SW
Department of Physiology, University of Toronto, Faculty of Medicine, University of Toronto Centre for the Study of Pain, Toronto, Ontario, Canada.
Vadakkan
Kunjumon I
KI
Ao
Hushan
H
Gallitano-Mendel
Amelia
A
Wei
Feng
F
Milbrandt
Jeffrey
J
Zhuo
Min
M
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000502:physiology; D006179:Gyrus Cinguli / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000235:genetics*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009619:Nociceptors / Q000502:physiology; D009924:Organ Culture Techniques; D010146:Pain / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D010812:Physical Stimulation; D011930:Reaction Time / Q000235:genetics; D013826:Theta Rhythm; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D014157:Transcription Factors