PMID- 25281204
OWN - NLM
STAT- MEDLINE
DCOM- 20150807
LR  - 20220408
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 744
DP  - 2014 Dec 5
TI  - NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic 
      stimulation.
PG  - 28-35
LID - S0014-2999(14)00690-6 [pii]
LID - 10.1016/j.ejphar.2014.09.034 [doi]
AB  - NMDA receptors (NMDAR) are important in the development and maintenance of 
      central sensitization. Our objective was to investigate the role of spinal 
      neurons and NMDAR in the maintenance of chronic visceral pain. Neonatal rats were 
      injected with acidic saline adjusted to pH 4.0 in the gastrocnemius muscle every 
      other day for 12 days. In adult rats, NR1 and NR2B subunits were examined in the 
      lumbo-sacral (LS) spinal cord. A baseline, visceromotor response (VMR) to graded 
      colorectal distension (CRD) was recorded before and after administration of the 
      NMDA antagonist, CGS-19755. Extracellular recordings were performed from 
      CRD-sensitive LS spinal neurons and pelvic nerve afferents (PNA) before and after 
      CGS-19755. Rats that received pH 4.0 saline injections demonstrated a significant 
      increase in the expression NR2B subunits and VMR response to CRD>20 mmHg. 
      CGS-19755 (i.v. or i.t.) had no effect in naive rats, but significantly decreased 
      the response to CRD in pH 4.0 saline injected rats. CGS-19755 had no effect on 
      the spontaneous firing of SL-A, but decreased that of SL-S. Similarly, CGS-19755 
      attenuates the responses of SL-S neurons to CRD, but had no effect on SL-A 
      neurons or on the response characteristics of PNA fibers. Neonatal noxious 
      somatic stimulation results in chronic visceral hyperalgesia and sensitizes a 
      specific subpopulation of CRD-sensitive spinal neurons. The sensitization of 
      these SL-S spinal neurons is attenuated by the NMDAR antagonist. The results of 
      this study suggest that spinal NMDARs play an important role in the development 
      of hyperalgesia early in life.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Miranda, Adrian
AU  - Miranda A
AD  - Division of Gastroenterology, Department of Pediatrics, Medical College of 
      Wisconsin, Milwaukee, WI 53226, United States. Electronic address: 
      amiranda@mcw.edu.
FAU - Mickle, Aaron
AU  - Mickle A
AD  - Division of Gastroenterology, Department of Pediatrics, Medical College of 
      Wisconsin, Milwaukee, WI 53226, United States.
FAU - Bruckert, Mitchell
AU  - Bruckert M
AD  - Division of Gastroenterology, Department of Pediatrics, Medical College of 
      Wisconsin, Milwaukee, WI 53226, United States.
FAU - Kannampalli, Pradeep
AU  - Kannampalli P
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, Medical 
      College of Wisconsin, Milwaukee, WI 53226, United States.
FAU - Banerjee, Banani
AU  - Banerjee B
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, Medical 
      College of Wisconsin, Milwaukee, WI 53226, United States.
FAU - Sengupta, Jyoti N
AU  - Sengupta JN
AD  - Division of Gastroenterology, Department of Pediatrics, Medical College of 
      Wisconsin, Milwaukee, WI 53226, United States; Division of Gastroenterology and 
      Hepatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 
      53226, United States.
LA  - eng
GR  - K08 DK076198/DK/NIDDK NIH HHS/United States
GR  - K08DK076198-01A1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140930
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Pipecolic Acids)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 4VGJ4A41L2 (selfotel)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Chronic Pain/chemically induced/*metabolism
MH  - Hyperalgesia/chemically induced/metabolism
MH  - Male
MH  - Neurons, Afferent/drug effects/*metabolism
MH  - Physical Stimulation/methods
MH  - Pipecolic Acids/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Spinal Cord/drug effects/*metabolism
MH  - Visceral Pain/chemically induced/*metabolism
PMC - PMC4261000
MID - NIHMS637800
OTO - NOTNLM
OT  - NMDA
OT  - Neonatal pain
OT  - Visceral hyperalgesia
EDAT- 2014/10/05 06:00
MHDA- 2015/08/08 06:00
PMCR- 2015/12/05
CRDT- 2014/10/05 06:00
PHST- 2014/04/09 00:00 [received]
PHST- 2014/09/22 00:00 [revised]
PHST- 2014/09/23 00:00 [accepted]
PHST- 2014/10/05 06:00 [entrez]
PHST- 2014/10/05 06:00 [pubmed]
PHST- 2015/08/08 06:00 [medline]
PHST- 2015/12/05 00:00 [pmc-release]
AID - S0014-2999(14)00690-6 [pii]
AID - 10.1016/j.ejphar.2014.09.034 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2014 Dec 5;744:28-35. doi: 10.1016/j.ejphar.2014.09.034. Epub 
      2014 Sep 30.