Are presynaptic GABA-Cρ2 receptors involved in anti-nociception?
We investigated the anti-nociceptive effects of GABA-C receptors in the central nervous system. Intracisternal injection of CACA, a GABA-C receptor agonist or isoguvacine, a GABA-A receptor agonist, significantly increased the tail-withdrawal latency. TPMPA, a GABA-C receptor antagonist blocked the effects of CACA but not isoguvacine indicating that GABA-C receptors are involved in regulating pain. Further, double-labelled immunofluorescence studies revealed that GABA-Cρ2 receptors are expressed presynaptically in the spinal dorsal horn, especially, substantia gelatinosa, a region that has been previously implicated in analgesia by regulating nociceptive inflow. These data provide a provenance for future work looking at presynaptic spinal GABA-C receptors in the control of nociception.
Neuroscience Research Laboratory, Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
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R
Tadavarty
Neuroscience Research Laboratory, Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada.
J
J
Hwang
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
P S
PS
Rajput
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
P J
PJ
Soja
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada.
U
U
Kumar
Neuroscience Research Laboratory, Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada. Electronic address: sastry@mail.ubc.ca.
B R
BR
Sastry
D000818:Animals; D003437:Crotonates / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D010721:Phosphinic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013376:Substantia Gelatinosa / Q000378:metabolism
C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D003437:Crotonates; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; C491397:Gabrr2 protein, rat; D007539:Isonicotinic Acids; D010721:Phosphinic Acids; D011725:Pyridines; D011963:Receptors, GABA-A; D017661:Receptors, Presynaptic; C015300:isoguvacine
Anti-nociception; Dorsal horn; GABA-C receptors; Pain; Spinal cord; Substantia gelatinosa