Reactive oxygen species are involved in group I mGluR-mediated facilitation of nociceptive processing in amygdala neurons.
Recent biochemical and behavioral data implicate reactive oxygen species (ROS) in peripheral and spinal pain mechanisms. However, pain-related functions of ROS in the brain and mechanisms of pain-related ROS activation remain to be determined. Our previous studies showed that the amygdala plays a key role in emotional-affective pain responses and pain modulation. Hyperactivity of amygdala neurons in an animal pain model depends on group I metabotropic glutamate receptors (subtypes mGluR1 and mGluR5), but their signaling pathway remains to be determined. Here we tested the hypothesis that activation of group I mGluRs increases nociceptive processing in amygdala neurons through a mechanism that involves ROS. Extracellular single-unit recordings were made from neurons in the laterocapsular division of the central nucleus of the amygdala (CeLC) in anesthetized adult male rats. Administration of a group I mGluR agonist (DHPG) into the CeLC by microdialysis increased the responses to innocuous and noxious somatosensory (knee joint compression) and visceral (colorectal distention [CRD]) stimuli. A ROS scavenger (PBN) and a superoxide dismutase mimetic (TEMPOL) reversed the facilitatory effects of DHPG. An mGluR5 antagonist (MPEP) also inhibited the effects of DHPG on the responses to innocuous and noxious somatosensory and visceral stimuli, whereas an mGluR1 antagonist (LY367385) decreased only the responses to visceral stimulation. The results show for the first time that ROS mediate group I mGluR-induced facilitation of nociceptive processing in amygdala neurons. The antagonist data may suggest differential contributions of subtypes mGluR1 and mGluR5 to the processing of somatosensory and visceral nociceptive information in the amygdala.
Ji
Guangchen
G
Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
Neugebauer
Volker
V
D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003106:Colon / Q000502:physiology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D055724:Electrophysiological Phenomena; D016166:Free Radical Scavengers / Q000494:pharmacology; D006614:Hindlimb / Q000502:physiology; D007596:Joints / Q000502:physiology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012007:Rectum / Q000502:physiology; D013113:Spin Labels
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D018094:Receptors, Metabotropic Glutamate; D013113:Spin Labels; C104077:metabotropic glutamate receptor type 1; D009569:Nitric Oxide; D008734:Methoxyhydroxyphenylglycol; D011493:Protein Kinase C; C001803:tempol; C010117:3,4-dihydroxyphenylglycol
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