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Increased C-fiber nociceptive input potentiates inhibitory glycinergic transmission in the spinal dorsal horn.
J Pharmacol Exp Ther. 2008 Mar; 324(3):1000-10.JP

Abstract

Glycine is an important inhibitory neurotransmitter in the spinal cord, but it also acts as a coagonist at the glycine site of N-methyl-d-aspartate (NMDA) receptors to potentiate nociceptive transmission. However, little is known about how increased nociceptive inflow alters synaptic glycine release in the spinal dorsal horn and its functional significance. In this study, we performed whole-cell recordings in rat lamina II neurons to record glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs). The transient receptor potential vanilloid receptor 1 agonist capsaicin caused a prolonged increase in the frequency of sIPSCs in 17 of 25 (68%) neurons tested. The potentiating effect of capsaicin on sIPSCs was blocked by ionotropic glutamate receptor antagonists or tetrodotoxin in most lamina II neurons examined. In contrast, the P2X agonist alphabeta-methylene-ATP increased sIPSCs in only two of 16 (12.5%) neurons. The glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic acid either increased or reduced the basal frequency of sIPSCs but did not significantly alter the potentiating effect of capsaicin on sIPSCs. Furthermore, the groups II and III metabotropic glutamate receptor antagonists had no significant effect on the capsaicin-induced increase in the sIPSC frequency. Although capsaicin reduced the amplitude of evoked excitatory postsynaptic currents at high stimulation currents, it did not change the ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/NMDA currents. This study provides the important new information that increased nociceptive inflow augments synaptic glycine release to spinal dorsal horn neurons through endogenous glutamate release. Potentiation of inhibitory glycinergic tone by stimulation of nociceptive primary afferents may function as a negative feedback mechanism to attenuate nociceptive transmission at the spinal level.

Authors+Show Affiliations

Department of Anesthesiology and Pain Medicine, Unit 110, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18079355

Citation

Zhou, Hong-Yi, et al. "Increased C-fiber Nociceptive Input Potentiates Inhibitory Glycinergic Transmission in the Spinal Dorsal Horn." The Journal of Pharmacology and Experimental Therapeutics, vol. 324, no. 3, 2008, pp. 1000-10.
Zhou HY, Zhang HM, Chen SR, et al. Increased C-fiber nociceptive input potentiates inhibitory glycinergic transmission in the spinal dorsal horn. J Pharmacol Exp Ther. 2008;324(3):1000-10.
Zhou, H. Y., Zhang, H. M., Chen, S. R., & Pan, H. L. (2008). Increased C-fiber nociceptive input potentiates inhibitory glycinergic transmission in the spinal dorsal horn. The Journal of Pharmacology and Experimental Therapeutics, 324(3), 1000-10.
Zhou HY, et al. Increased C-fiber Nociceptive Input Potentiates Inhibitory Glycinergic Transmission in the Spinal Dorsal Horn. J Pharmacol Exp Ther. 2008;324(3):1000-10. PubMed PMID: 18079355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased C-fiber nociceptive input potentiates inhibitory glycinergic transmission in the spinal dorsal horn. AU - Zhou,Hong-Yi, AU - Zhang,Hong-Mei, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, Y1 - 2007/12/13/ PY - 2007/12/15/pubmed PY - 2008/3/25/medline PY - 2007/12/15/entrez SP - 1000 EP - 10 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 324 IS - 3 N2 - Glycine is an important inhibitory neurotransmitter in the spinal cord, but it also acts as a coagonist at the glycine site of N-methyl-d-aspartate (NMDA) receptors to potentiate nociceptive transmission. However, little is known about how increased nociceptive inflow alters synaptic glycine release in the spinal dorsal horn and its functional significance. In this study, we performed whole-cell recordings in rat lamina II neurons to record glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs). The transient receptor potential vanilloid receptor 1 agonist capsaicin caused a prolonged increase in the frequency of sIPSCs in 17 of 25 (68%) neurons tested. The potentiating effect of capsaicin on sIPSCs was blocked by ionotropic glutamate receptor antagonists or tetrodotoxin in most lamina II neurons examined. In contrast, the P2X agonist alphabeta-methylene-ATP increased sIPSCs in only two of 16 (12.5%) neurons. The glutamate transporter inhibitor l-trans-pyrrolidine-2,4-dicarboxylic acid either increased or reduced the basal frequency of sIPSCs but did not significantly alter the potentiating effect of capsaicin on sIPSCs. Furthermore, the groups II and III metabotropic glutamate receptor antagonists had no significant effect on the capsaicin-induced increase in the sIPSC frequency. Although capsaicin reduced the amplitude of evoked excitatory postsynaptic currents at high stimulation currents, it did not change the ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/NMDA currents. This study provides the important new information that increased nociceptive inflow augments synaptic glycine release to spinal dorsal horn neurons through endogenous glutamate release. Potentiation of inhibitory glycinergic tone by stimulation of nociceptive primary afferents may function as a negative feedback mechanism to attenuate nociceptive transmission at the spinal level. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/18079355/Increased_C_fiber_nociceptive_input_potentiates_inhibitory_glycinergic_transmission_in_the_spinal_dorsal_horn_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=18079355 DB - PRIME DP - Unbound Medicine ER -