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NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation. Eur J Pharmacol 2014 Dec 05;744:28-35 PMID: 25281204 PMCID: PMC4261000


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 naïve 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.

Author List

Miranda A, Mickle A, Bruckert M, Kannampalli P, Banerjee B, Sengupta JN


Banani Banerjee PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Adrian Miranda MD Professor in the Pediatrics department at Medical College of Wisconsin
Jyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals, Newborn
Neurons, Afferent
Physical Stimulation
Pipecolic Acids
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Spinal Cord

View this publication's entry at the Pubmed website PMID: 25281204
jenkins-FCD Prod-141 f776ee82366dc5656a368d51cce32734d2f9b9a0