PMID- 29496640
OWN - NLM
STAT- MEDLINE
DCOM- 20191111
LR  - 20191111
IS  - 1528-8447 (Electronic)
IS  - 1526-5900 (Print)
IS  - 1526-5900 (Linking)
VI  - 19
IP  - 7
DP  - 2018 Jul
TI  - Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral 
      Hypersensitivity in Rats.
PG  - 764-776
LID - S1526-5900(18)30087-7 [pii]
LID - 10.1016/j.jpain.2018.02.007 [doi]
AB  - Chronic stress produces maladaptive pain responses, manifested as alterations in 
      pain processing and exacerbation of chronic pain conditions including irritable 
      bowel syndrome. Female predominance, especially during reproductive years, 
      strongly suggests a role of gonadal hormones. However, gonadal hormone modulation 
      of stress-induced pain hypersensitivity is not well understood. In the present 
      study, we tested the hypothesis that estradiol is pronociceptive and testosterone 
      is antinociceptive in a model of stress-induced visceral hypersensitivity (SIVH) 
      in rats by recording the visceromotor response to colorectal distention after a 
      3-day forced swim (FS) stress paradigm. FS induced visceral hypersensitivity that 
      persisted at least 2 weeks in female, but only 2 days in male rats. Ovariectomy 
      blocked and orchiectomy facilitated SIVH. Furthermore, estradiol injection in 
      intact male rats increased SIVH and testosterone in intact female rats attenuated 
      SIVH. Western blot analyses indicated estradiol increased excitatory glutamate 
      ionotropic receptor NMDA type subunit 1 expression and decreased inhibitory 
      metabotropic glutamate receptor 2 expression after FS in male thoracolumbar 
      spinal cord. In addition, the presence of estradiol during stress increased 
      spinal brain-derived neurotrophic factor (BDNF) expression independent of sex. In 
      contrast, testosterone blocked the stress-induced increase in BDNF expression in 
      female rats. These data suggest that estradiol facilitates and testosterone 
      attenuates SIVH by modulating spinal excitatory and inhibitory glutamatergic 
      receptor expression. PERSPECTIVE: SIVH is more robust in female rats. Estradiol 
      facilitates whereas testosterone dampens the development of SIVH. This could 
      partially explain the greater prevalence of certain chronic visceral pain 
      conditions in women. An increase in spinal BDNF is concomitant with increased 
      stress-induced pain. Pharmaceutical interventions targeting this molecule could 
      provide promising alleviation of SIVH in women.
CI  - Copyright (c) 2018 The American Pain Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Ji, Yaping
AU  - Ji Y
AD  - Department of Neural and Pain Sciences, School of Dentistry, University of 
      Maryland Baltimore, Baltimore, Maryland; University of Maryland Center to Advance 
      Chronic Pain Research, Baltimore, Maryland.
FAU - Hu, Bo
AU  - Hu B
AD  - Department of Neural and Pain Sciences, School of Dentistry, University of 
      Maryland Baltimore, Baltimore, Maryland; Key laboratory of Shaanxi Province for 
      Craniofacial Precision Medicine Research, Xi'an Jiaotong University College of 
      Stomatology, Xi'an, Shaanxi, China.
FAU - Li, Jiyun
AU  - Li J
AD  - Department of Neural and Pain Sciences, School of Dentistry, University of 
      Maryland Baltimore, Baltimore, Maryland.
FAU - Traub, Richard J
AU  - Traub RJ
AD  - Department of Neural and Pain Sciences, School of Dentistry, University of 
      Maryland Baltimore, Baltimore, Maryland; University of Maryland Center to Advance 
      Chronic Pain Research, Baltimore, Maryland. Electronic address: 
      rtraub@umaryland.edu.
LA  - eng
GR  - R01 NR015472/NR/NINR NIH HHS/United States
GR  - R01 NS037424/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180302
PL  - United States
TA  - J Pain
JT  - The journal of pain
JID - 100898657
RN  - 3XMK78S47O (Testosterone)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Estradiol/*metabolism
MH  - Female
MH  - Hyperalgesia/*metabolism/physiopathology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Sex Characteristics
MH  - Stress, Psychological/*metabolism/physiopathology
MH  - Testosterone/*metabolism
MH  - Visceral Pain/metabolism/physiopathology
PMC - PMC6026052
MID - NIHMS946233
OTO - NOTNLM
OT  - Stress
OT  - estradiol
OT  - hyperalgesia
OT  - testosterone
OT  - visceral pain
COIS- Disclosures: The authors have nothing to declare and have no conflicts of 
      interest.
EDAT- 2018/03/03 06:00
MHDA- 2019/11/12 06:00
PMCR- 2019/07/01
CRDT- 2018/03/03 06:00
PHST- 2017/08/31 00:00 [received]
PHST- 2018/01/30 00:00 [revised]
PHST- 2018/02/14 00:00 [accepted]
PHST- 2018/03/03 06:00 [pubmed]
PHST- 2019/11/12 06:00 [medline]
PHST- 2018/03/03 06:00 [entrez]
PHST- 2019/07/01 00:00 [pmc-release]
AID - S1526-5900(18)30087-7 [pii]
AID - 10.1016/j.jpain.2018.02.007 [doi]
PST - ppublish
SO  - J Pain. 2018 Jul;19(7):764-776. doi: 10.1016/j.jpain.2018.02.007. Epub 2018 Mar 
      2.