Does intravenous administration of GABA(A) receptor antagonists induce both descending antinociception and touch-evoked allodynia?
Effects of intravenous administration of picrotoxin (PTX), a GABA(A) receptor antagonist, upon activities of wide dynamic range (WDR) neurons in the lumbar spinal cord were studied in urethane-chloralose anesthetized cats. Intravenous PTX augmented tactile evoked responses of WDR neurons, but reduced nociceptive responses dose-dependently. Spinal transection reversed the suppression of nociceptive responses. In the spinal cat, intravenous PTX enhanced the tactile evoked response. Intravenous PTX enhanced the spontaneous firing of nucleus raphe dorsalis (NRD) and/or ventral periaqueductal gray (PAG) neurons projecting to nucleus raphe magnus. Lidocaine injected into NRD/PAG reversed the antinociceptive action of intravenous PTX. PTX injected into NRD/PAG reduced heat-evoked responses of WDR units. These data suggest that antinociceptive effects of intravenous PTX is primarily due to disinhibitory activation of the descending antinociceptive system originating from NRD and PAG, and that PTX reinforces touch-evoked responses in the spinal cord.
Department of Physiology, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan.
Natsu
N
Koyama
Fumihiko
F
Hanai
Toshikatsu
T
Yokota
D000700:Analgesics / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001931:Brain Mapping; D002415:Cats; D003655:Decerebrate State; D004594:Electrophysiology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D006358:Hot Temperature; D008012:Lidocaine / Q000494:pharmacology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects; D010146:Pain / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000503:physiopathology; D010812:Physical Stimulation; D010852:Picrotoxin / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D014110:Touch / Q000187:drug effects / Q000502:physiology*
D000700:Analgesics; D000779:Anesthetics, Local; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D008012:Lidocaine; D010852:Picrotoxin