Peripheral inflammation sensitizes P2X receptor-mediated responses in rat dorsal root ganglion neurons.
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.
Xu
Guang-Yin
GY
Marine Biomedical Institute and Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
Huang
Li-Yen Mae
LY
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D015153:Blotting, Western; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism*
D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D005620:Freund's Adjuvant; C002630:alpha,beta-methyleneadenosine 5'-triphosphate