title: Hypertonic saline-induced muscle nociception and c-fos activation are partially mediated by peripheral NMDA receptors.
abstract: In this study, the animal model of hypertonic saline (HS) infusion protocol was developed and utilized to test the hypothesis that HS causes peripheral release of glutamate, and that blockade of peripheral NMDA receptors significantly reduces HS-induced nocifensive behavior and central neuronal activation. Nocifensive behavior and c-fos immunoreactivity, as a marker of central neuronal activation, were assessed from the animals that received intramuscular HS infusion with and without the NMDA receptor antagonist, MK-801. HS infusion (20 microl/min for 10 min) in the rat masseter produced prolonged nocifensive hindpaw shaking responses that peaked in the first minute and gradually diminished over the infusion period. The HS induced nocifensive behavior was dose-dependently attenuated by MK-801 pretreatments (0.3 mg/kg and 0.1 mg/kg), but not by vehicle pretreatment (isotonic saline; ISO), in the masseter muscle. HS infusion produced a significant number of Fos positive neurons in the ispsilateral subnucleus caudalis (Vc). Subsequent immunohistochemical studies showed that peripheral MK-801 pretreatment effectively reduced the HS induced neuronal activation in the Vc. These results provide compelling evidence that HS-induced muscle nociception is mediated, in part, by peripheral release of glutamate, and that blockade of peripheral glutamate receptors may provide effective means of preventing central neuronal activation.
authors.affiliation: University of Maryland Baltimore, School of Dentistry, Department of Biomedical Sciences, 666 W. Baltimore Street, Baltimore, MD 21201, USA. jro@umaryland.edu
authors.forename: Jin Y
authors.initials: JY
authors.lastname: Ro
authors.forename: Norman F
authors.initials: NF
authors.lastname: Capra
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Radi
authors.initials: R
authors.lastname: Masri
authors.forename: Yang-Hyun
authors.initials: YH
authors.lastname: Chun
mesh_terms: D000818:Animals; D015415:Biomarkers; D001933:Brain Stem / Q000502:physiology; D003627:Data Interpretation, Statistical; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005950:Glucose Solution, Hypertonic / Q000008:administration & dosage; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D008297:Male; D008406:Masseter Muscle / Q000502:physiology*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000235:genetics; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000139:chemically induced* / Q000235:genetics; D017933:Peripheral Nervous System / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D014278:Trigeminal Nuclei / Q000502:physiology
chemical_list: D015415:Biomarkers; D018691:Excitatory Amino Acid Antagonists; D005950:Glucose Solution, Hypertonic; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate