title: Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.
abstract: Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG) one week following a chronic constriction injury (CCI) of the sciatic nerve in adult rats. We found that small diameter DRG neurons (<30 µm) exhibited increased excitability that was associated with decreased membrane threshold and rheobase, whereas responses in large diameter neurons (>30 µm) were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid (KA), or the group I metabotropic receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG), induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA)-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California, United States of America; Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Kerui
authors.initials: K
authors.lastname: Gong
authors.affiliation: Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Ling-Hsuan
authors.initials: LH
authors.lastname: Kung
authors.affiliation: Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America; Department of Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Giulia
authors.initials: G
authors.lastname: Magni
authors.affiliation: Department of Surgery, University of California San Francisco, San Francisco, California, United States of America; Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Aditi
authors.initials: A
authors.lastname: Bhargava
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California, United States of America; Department of Anatomy, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Luc
authors.initials: L
authors.lastname: Jasmin
mesh_terms: D000200:Action Potentials; D000818:Animals; D003514:Cyclohexylamines / Q000494:pharmacology; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
chemical_list: D003514:Cyclohexylamines; D018698:Glutamic Acid; D007608:Kainic Acid; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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