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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.EJ

Abstract

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.

Authors+Show Affiliations

Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States. Electronic address: amiranda@mcw.edu.Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, United States.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.Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25281204

Citation

Miranda, Adrian, et al. "NMDA Receptor Mediates Chronic Visceral Pain Induced By Neonatal Noxious Somatic Stimulation." European Journal of Pharmacology, vol. 744, 2014, pp. 28-35.
Miranda A, Mickle A, Bruckert M, et al. NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation. Eur J Pharmacol. 2014;744:28-35.
Miranda, A., Mickle, A., Bruckert, M., Kannampalli, P., Banerjee, B., & Sengupta, J. N. (2014). NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation. European Journal of Pharmacology, 744, 28-35. https://doi.org/10.1016/j.ejphar.2014.09.034
Miranda A, et al. NMDA Receptor Mediates Chronic Visceral Pain Induced By Neonatal Noxious Somatic Stimulation. Eur J Pharmacol. 2014 Dec 5;744:28-35. PubMed PMID: 25281204.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NMDA receptor mediates chronic visceral pain induced by neonatal noxious somatic stimulation. AU - Miranda,Adrian, AU - Mickle,Aaron, AU - Bruckert,Mitchell, AU - Kannampalli,Pradeep, AU - Banerjee,Banani, AU - Sengupta,Jyoti N, Y1 - 2014/09/30/ PY - 2014/04/09/received PY - 2014/09/22/revised PY - 2014/09/23/accepted PY - 2014/10/5/entrez PY - 2014/10/5/pubmed PY - 2015/8/8/medline KW - NMDA KW - Neonatal pain KW - Visceral hyperalgesia SP - 28 EP - 35 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 744 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25281204/NMDA_receptor_mediates_chronic_visceral_pain_induced_by_neonatal_noxious_somatic_stimulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00690-6 DB - PRIME DP - Unbound Medicine ER -