 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, March 1, 2001, 21(5):1750-1756
Direct Activation of Rat Spinal Dorsal Horn Neurons by Prostaglandin E2
Hiroshi Baba, Tatsuro Kohno, Kimberly A. Moore, and Clifford J. Woolf Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129
Whole-cell patch-clamp and intracellular recording techniques have been used to study the action of prostaglandin E2 (PGE2) on neurons in adult rat transverse spinal cord slices. Bath-applied PGE2 (1-20 µM) induced an inward current or membrane depolarization in the majority of deep dorsal horn neurons (laminas III-VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2 alone never elicited spontaneous action potentials; however, it did convert subthreshold EPSPs to suprathreshold, leading to action potential generation. PGE2-induced inward currents were unaffected by perfusion with either a Ca2+-free/high Mg2+ (5 mM) solution or tetrodotoxin (1 µM), indicating a direct postsynaptic action. Both 17-phenyl trinor prostaglandin E2 (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect on membrane current, whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2. Depolarizing responses to PGE2 were associated with a decrease in input resistance, and the amplitude of inward current was decreased as the holding potential was depolarized. PGE2-induced inward currents were reduced by substitution of extracellular Na+ with N-methyl-D-glucamine and inhibited by flufenamic acid (50-200 µM), which is compatible with activation of a nonselective cation channel. These results suggest that PGE2, acting via an EP2-like receptor, directly depolarizes spinal neurons. Moreover, these findings imply an involvement of spinal cord-generated prostanoids in modulating sensory processing through an alteration in dorsal horn neuronal excitability.
Key words: inflammation; central sensitization; prostaglandin E2; EP2 receptor; deep dorsal horn; allodynia; hyperalgesia
Copyright © 2001 Society for Neuroscience 0270-6474/01/2151750-07$05.00/0
This article has been cited by other articles:
H. Beloeil, M. Gentili, D. Benhamou, and J.-X. Mazoit
The Effect of a Peripheral Block on Inflammation-Induced Prostaglandin E2 and Cyclooxygenase Expression in Rats
Anesth. Analg., September 1, 2009; 109(3): 943 - 950.
[Abstract] [Full Text] [PDF]
T. Fujita, T. Liu, T. Nakatsuka, and E. Kumamoto
Proteinase-Activated Receptor-1 Activation Presynaptically Enhances Spontaneous Glutamatergic Excitatory Transmission in Adult Rat Substantia Gelatinosa Neurons
J Neurophysiol, July 1, 2009; 102(1): 312 - 319.
[Abstract] [Full Text] [PDF]
V. Umbrain, L. Shi, M.-H. Lauwers, I. Smolders, Y. Michotte, and F. Camu
Intrathecal lidocaine elevates prostaglandin E2 levels in cerebrospinal fluid: a microdialysis study in freely moving rats
Br. J. Anaesth., November 1, 2008; 101(5): 716 - 722.
[Abstract] [Full Text] [PDF]
T. Liu, T. Fujita, T. Nakatsuka, and E. Kumamoto
Phospholipase A2 Activation Enhances Inhibitory Synaptic Transmission in Rat Substantia Gelatinosa Neurons
J Neurophysiol, March 1, 2008; 99(3): 1274 - 1284.
[Abstract] [Full Text] [PDF]
D. V. Vasilyev, Q. Shan, Y. Lee, S. C. Mayer, M. R. Bowlby, B. W. Strassle, E. J. Kaftan, K. E. Rogers, and J. Dunlop
Direct Inhibition of Ih by Analgesic Loperamide in Rat DRG Neurons
J Neurophysiol, May 1, 2007; 97(5): 3713 - 3721.
[Abstract] [Full Text] [PDF]
M. Bianchi, C. Martucci, P. Ferrario, S. Franchi, and P. Sacerdote
Increased Tumor Necrosis Factor-{alpha} and Prostaglandin E2 Concentrations in the Cerebrospinal Fluid of Rats with Inflammatory Hyperalgesia: The Effects of Analgesic Drugs
Anesth. Analg., April 1, 2007; 104(4): 949 - 954.
[Abstract] [Full Text] [PDF]
P. Zhao, S. G. Waxman, and B. C. Hains
Extracellular Signal-Regulated Kinase-Regulated Microglia-Neuron Signaling by Prostaglandin E2 Contributes to Pain after Spinal Cord Injury
J. Neurosci., February 28, 2007; 27(9): 2357 - 2368.
[Abstract] [Full Text] [PDF]
J. H. Sun, B. Yang, D. F. Donnelly, C. Ma, and R. H. LaMotte
MCP-1 Enhances Excitability of Nociceptive Neurons in Chronically Compressed Dorsal Root Ganglia
J Neurophysiol, November 1, 2006; 96(5): 2189 - 2199.
[Abstract] [Full Text] [PDF]
N. Sang and C. Chen
Lipid Signaling and Synaptic Plasticity
Neuroscientist, October 1, 2006; 12(5): 425 - 434.
[Abstract] [PDF]
J. S. Kroin, A. Buvanendran, D. E. Watts, C. Saha, and K. J. Tuman
Upregulation of cerebrospinal fluid and peripheral prostaglandin E2 in a rat postoperative pain model.
Anesth. Analg., August 1, 2006; 103(2): 334 - 43, table of contents.
[Abstract] [Full Text] [PDF]
N. Sang, J. Zhang, V. Marcheselli, N. G. Bazan, and C. Chen
Postsynaptically Synthesized Prostaglandin E2 (PGE2) Modulates Hippocampal Synaptic Transmission via a Presynaptic PGE2 EP2 Receptor
J. Neurosci., October 26, 2005; 25(43): 9858 - 9870.
[Abstract] [Full Text] [PDF]
K.-J. Won, K. M. Sanders, and S. M. Ward
Interstitial cells of Cajal mediate mechanosensitive responses in the stomach
PNAS, October 11, 2005; 102(41): 14913 - 14918.
[Abstract] [Full Text] [PDF]
A. Hofacker, O. Coste, H.-V. Nguyen, C. Marian, K. Scholich, and G. Geisslinger
Downregulation of Cytosolic Prostaglandin E2 Synthase Results in Decreased Nociceptive Behavior in Rats
J. Neurosci., September 28, 2005; 25(39): 9005 - 9009.
[Abstract] [Full Text] [PDF]
C. Chen and N. G. Bazan
Endogenous PGE2 Regulates Membrane Excitability and Synaptic Transmission in Hippocampal CA1 Pyramidal Neurons
J Neurophysiol, February 1, 2005; 93(2): 929 - 941.
[Abstract] [Full Text] [PDF]
R. J. Harvey, U. B. Depner, H. Wassle, S. Ahmadi, C. Heindl, H. Reinold, T. G. Smart, K. Harvey, B. Schutz, O. M. Abo-Salem, et al.
GlyR {alpha}3: An Essential Target for Spinal PGE2-Mediated Inflammatory Pain Sensitization
Science, May 7, 2004; 304(5672): 884 - 887.
[Abstract] [Full Text] [PDF]
J. R. Ghilardi, C. I. Svensson, S. D. Rogers, T. L. Yaksh, and P. W. Mantyh
Constitutive Spinal Cyclooxygenase-2 Participates in the Initiation of Tissue Injury-Induced Hyperalgesia
J. Neurosci., March 17, 2004; 24(11): 2727 - 2732.
[Abstract] [Full Text] [PDF]
K.-J. Bar, G. Natura, A. Telleria-Diaz, P. Teschner, R. Vogel, E. Vasquez, H.-G. Schaible, and A. Ebersberger
Changes in the Effect of Spinal Prostaglandin E2 during Inflammation: Prostaglandin E (EP1-EP4) Receptors in Spinal Nociceptive Processing of Input from the Normal or Inflamed Knee Joint
J. Neurosci., January 21, 2004; 24(3): 642 - 651.
[Abstract] [Full Text] [PDF]
G. S. Jelson, G. M. DeMasi, K. L. Sager, and J. C. Hardwick
Modulation of guinea pig intrinsic cardiac neurons by prostaglandins
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R682 - R689.
[Abstract] [Full Text] [PDF]
D. R. Conklin and J. C. Eisenach
Intrathecal Ketorolac Enhances Antinociception from Clonidine
Anesth. Analg., January 1, 2003; 96(1): 191 - 194.
[Abstract] [Full Text] [PDF]
B. Hinz and K. Brune
Cyclooxygenase-2---10 Years Later
J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 367 - 375.
[Abstract] [Full Text] [PDF]
E. Vasquez, K.-J. Bar, A. Ebersberger, B. Klein, H. Vanegas, and H.-G. Schaible
Spinal Prostaglandins Are Involved in the Development But Not the Maintenance of Inflammation-Induced Spinal Hyperexcitability
J. Neurosci., November 15, 2001; 21(22): 9001 - 9008.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|