PMID- 21392887
OWN - NLM
STAT- MEDLINE
DCOM- 20110823
LR  - 20220310
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Print)
IS  - 0304-3959 (Linking)
VI  - 152
IP  - 5
DP  - 2011 May
TI  - Spinal estrogen receptor alpha mediates estradiol-induced pronociception in a 
      visceral pain model in the rat.
PG  - 1182-1191
LID - 10.1016/j.pain.2011.01.046 [doi]
AB  - We previously reported that 17beta-estradiol (E2) is pronociceptive in a visceral 
      pain model in the rat. Subcutaneously (s.c.) administered E2 reversed the 
      decrease in the colorectal distention (CRD)-evoked visceromotor response produced 
      by ovariectomy (OVx) and CRD-induced nociceptive responses were greater in 
      proestrous rats compared with met/diestrous rats. The site of action, the type of 
      estrogen receptors activated, and the possible intracellular signaling pathway 
      involved are yet to be established. In the present study, intrathecal (i.t.) E2 
      administered to OVx rats mimicked the effects of s.c. E2, suggesting that spinal 
      estrogen receptors are involved. This is further supported by the observations 
      that the anti-estrogen ICI 182,780 injected i.t. in intact female rats 
      significantly decreased the visceromotor response to CRD, the response of colonic 
      afferents was not affected by OVx, and colonic afferents did not label for 
      estrogen receptor alpha (ERalpha). The ERalpha selective agonist, 
      4,4',4''-[4-propyl-(1H)-pyrazole-1,3,5-triyl]tris-phenol (PPT; s.c. or i.t.) 
      facilitated the visceromotor response similar to E2, suggesting ERalpha activation is 
      involved in mediating the pronociceptive effect of E2. PPT (s.c. or i.t.) 
      increased the response of spinal dorsal horn neurons to CRD, indicating a spinal 
      site of action. In addition, s.c. E2 or PPT increased CRD-induced spinal 
      extracellular signal-regulated kinase (ERK) phosphorylation that was not observed 
      in OVx rats and a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor 
      blocked facilitation of the visceromotor response by PPT. Taken together, the 
      present study demonstrates that spinal ERalpha mediates the pronociceptive effect of 
      E2 on visceral signal processing through activation of the MAPK pathway.
CI  - Copyright (c) 2011 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Ji, Yaping
AU  - Ji Y
AD  - Department of Neural and Pain Sciences, University of Maryland Dental School, 
      Baltimore, MD, USA.
FAU - Tang, Bin
AU  - Tang B
FAU - Traub, Richard J
AU  - Traub RJ
LA  - eng
GR  - R01 NS037424/NS/NINDS NIH HHS/United States
GR  - R01 NS037424-09/NS/NINDS NIH HHS/United States
GR  - R01 NS 37424/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110309
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Estrogen Antagonists)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Estrogens)
RN  - 0 (Ginsenosides)
RN  - 0 (Sapogenins)
RN  - 0 (ginsenoside 20S-protopanaxatriol)
RN  - 22X328QOC4 (Fulvestrant)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Afferent Pathways/physiology
MH  - Analysis of Variance
MH  - Animals
MH  - Colon/innervation
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Estradiol/adverse effects/analogs & derivatives/therapeutic use
MH  - Estrogen Antagonists/therapeutic use
MH  - Estrogen Receptor alpha/*metabolism
MH  - Estrogens/adverse effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Fulvestrant
MH  - Ginsenosides/adverse effects
MH  - Ovariectomy
MH  - Pain/drug therapy/*etiology/metabolism/*pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sapogenins/adverse effects
MH  - Spinal Cord/*metabolism
MH  - Viscera/*innervation/*metabolism
PMC - PMC3079062
MID - NIHMS270202
EDAT- 2011/03/12 06:00
MHDA- 2011/08/24 06:00
PMCR- 2012/05/01
CRDT- 2011/03/12 06:00
PHST- 2010/07/07 00:00 [received]
PHST- 2011/01/21 00:00 [revised]
PHST- 2011/01/24 00:00 [accepted]
PHST- 2011/03/12 06:00 [entrez]
PHST- 2011/03/12 06:00 [pubmed]
PHST- 2011/08/24 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - 00006396-201105000-00033 [pii]
AID - 10.1016/j.pain.2011.01.046 [doi]
PST - ppublish
SO  - Pain. 2011 May;152(5):1182-1191. doi: 10.1016/j.pain.2011.01.046. Epub 2011 Mar 
      9.