Increased nociceptive input rapidly modulates spinal GABAergic transmission through endogenously released glutamate.
Stimulation of nociceptive primary afferents elicits pain by promoting glutamatergic transmission in the spinal cord. Little is known about how increased nociceptive input controls GABAergic tone in the spinal dorsal horn. In this study, we determined how increased nociceptive inflow affects GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) of lamina II neurons by using whole cell recordings in rat spinal cord slices. Bath application of capsaicin for 3 min induced a long-lasting inhibition of sIPSCs in 50% of the neurons tested. In the other half of the neurons, capsaicin either increased the frequency of sIPSCs (34.6%) or had no effect on sIPSCs (15.4%). The GABA(A) current elicited by puff application of GABA was not altered by capsaicin. Capsaicin did not inhibit sIPSCs in rats treated with intrathecal pertussis toxin. Also, capsaicin failed to inhibit sIPSCs in the presence of ionotropic glutamate receptor antagonists or in the presence of both LY341495 and CPPG (group II and group III metabotropic glutamate receptor antagonists, respectively). However, when LY341495 or CPPG was used alone, capsaicin still decreased the frequency of sIPSCs in some neurons. Additionally, bradykinin significantly inhibited sIPSCs in a population of lamina II neurons and this inhibitory effect was also abolished by LY341495 and CPPG. Our study provides novel information that stimulation of nociceptive primary afferents rapidly suppresses GABAergic input to many dorsal horn neurons through endogenous glutamate and activation of presynaptic group II and group III metabotropic glutamate receptors. These findings extend our understanding of the microcircuitry of the spinal dorsal horn involved in nociception.
Zhou
Hong-Yi
HY
Department of Anesthesiology and Pain Medicine, Unit 409, The University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Blvd., Houston, TX 77030, USA.
Zhang
Hong-Mei
HM
Chen
Shao-Rui
SR
Pan
Hui-Lin
HL
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D037342:Pertussis Toxin / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D011963:Receptors, GABA-A; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D037342:Pertussis Toxin; D002211:Capsaicin