title: N-methyl-D-aspartate receptor agonism and antagonism within the amygdaloid central nucleus suppresses pain affect: differential contribution of the ventrolateral periaqueductal gray.
abstract: The amygdala contributes to the generation of pain affect, and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study compared the contribution of N-methyl-d-aspartate (NMDA) receptor agonism and antagonism in the CeA to generation of the affective response of rats to an acute noxious stimulus. Vocalizations that occur following a brief tail shock (vocalization afterdischarges) are a validated rodent model of pain affect and were preferentially suppressed, in a dose-dependent manner, by bilateral injection into the CeA of NMDA (.1, .25, .5, or 1 μg/side) or the NMDA receptor antagonist d-(-)-2-amino-5-phosphopentanoic acid (AP5; 1, 2, or 4 μg/side). Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of NMDA or AP5 into the CeA. Injection of NMDA, but not AP5, into the CeA increased c-Fos immunoreactivity in the ventrolateral periaqueductal gray, and unilateral injection of the μ-opiate receptor antagonist H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; .25 μg) into ventrolateral periaqueductal gray prevented the antinociception generated by injection of NMDA into the CeA. These findings demonstrate that although NMDA receptor agonism and antagonism in the CeA produce similar suppression of pain behaviors, they do so via different neurobiologic mechanisms.
  
  
  CONCLUSIONS
  The amygdala contributes to production of the emotional dimension of pain. NMDA receptor agonism and antagonism within the CeA suppressed rats' emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders.
authors.affiliation: Department of Psychology, Behavioral & Cognitive Neuroscience Program, Wayne State University, Detroit, Michigan.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Spuz
authors.affiliation: Department of Psychology, Behavioral & Cognitive Neuroscience Program, Wayne State University, Detroit, Michigan.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Tomaszycki
authors.affiliation: Department of Psychology, Behavioral & Cognitive Neuroscience Program, Wayne State University, Detroit, Michigan. Electronic address: borszcz@wayne.edu.
authors.forename: George S
authors.initials: GS
authors.lastname: Borszcz
mesh_terms: D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D058748:Pain Perception / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014828:Vocalization, Animal
chemical_list: C529311:CTAP octapeptide; D009292:Narcotic Antagonists; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; D013004:Somatostatin; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
keywords: NMDA; Nociception; amygdala; c-Fos; emotion; glutamate; periaqueductal gray; vocalization