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The Journal of Neuroscience, January 1, 2002, 22(1):93-102
Peripheral Inflammation Sensitizes P2X Receptor-Mediated
Responses in Rat Dorsal Root Ganglion Neurons
Guang-Yin
Xu1 and
Li-Yen Mae
Huang1, 2
1 Marine Biomedical Institute and
2 Department of Physiology and Biophysics, University of
Texas Medical Branch, Galveston, Texas 77555-1069
ATP-gated P2X receptors in nociceptive sensory neurons participate
in transmission of pain signals from the periphery to the spinal cord.
To determine the role of P2X receptors under injurious conditions, we
examined ATP-evoked responses in dorsal root ganglion (DRG) neurons
isolated from rats with peripheral inflammation, induced by injections
of complete Freund's adjuvant (CFA) into the hindpaw. Application of
ATP induced both fast- and slow-inactivating currents in control and
inflamed neurons. CFA treatment had no effect on the affinity of ATP
for its receptors or receptor phenotypes. On the other hand,
inflammation caused a twofold to threefold increase in both
ATP-activated currents, altered the voltage dependence of P2X
receptors, and enhanced the expression of P2X2 and P2X3 receptors. The
increase in ATP responses gave rise to large depolarizations that
exceeded the threshold of action potentials in inflamed DRG neurons.
Thus, P2X receptor upregulation could account for neuronal hypersensitivity and contribute to abnormal pain responses associated with inflammatory injuries. These results suggest that P2X receptors are useful targets for inflammatory pain therapy.
Key words:
dorsal root ganglion; ATP; P2X receptor; Western
blotting; peripheral inflammation; pain; electrophysiology
Copyright © 2002 Society for Neuroscience 0270-6474/02/22193-10$05.00/0
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