Peripheral inhibition of glutaminase reduces carrageenan-induced Fos expression in the superficial dorsal horn of the rat

Ernest M. Hoffman, Kenneth Miller

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In inflamed tissue, the levels of the excitatory amino acid glutamate are increased. Glutamate sensitizes peripheral axons of primary afferent neurons during inflammation leading to decreased firing threshold and hyperexcitability. One proposed source of glutamate is the primary afferent. Antagonizing glutamate receptors on peripheral axons of primary afferents during inflammation provides analgesia in animals and humans. The enzyme glutaminase is used by primary sensory neurons to convert glutamine to glutamate, and peripheral inhibition of glutaminase with 6-diazo-5-oxo-l-norleucine (DON) provides long-lasting analgesia during inflammation. In this study, we measured the effects of glutaminase inhibition on carrageenan-induced spinal Fos expression. Rats were given intraplantar injections of carrageenan and treated locally with either vehicle or DON. After 3 h of inflammation, hind paw swelling and spinal expression of Fos were examined. CellProfiler was used to automate Fos nuclei counting in five laminar groupings in the spinal cord (I-II, III-IV, V-VI, VII-IX, X). Carrageenan increased hind paw thickness by ∼70% and spinal Fos expression in superficial (I-II) and deep (V-VI) laminae by 10-fold and 5-fold, respectively. Treatment with DON reduced hind paw swelling by ∼13% and suppressed Fos expression in the laminae I-II by ∼54%, but not the deep laminae. Our results further support the notion of glutamate as a peripheral inflammatory mediator and indicate that glutaminase should be considered as a novel therapeutic target for treatment of inflammatory pain.

Original languageEnglish
Pages (from-to)157-160
Number of pages4
JournalNeuroscience Letters
Volume472
Issue number3
DOIs
StatePublished - 26 Mar 2010

Fingerprint

Glutaminase
Carrageenan
Diazooxonorleucine
Glutamic Acid
Inflammation
Analgesia
Axons
Afferent Neurons
Excitatory Amino Acids
Glutamate Receptors
Sensory Receptor Cells
Glutamine
Spinal Cord
Therapeutics
Spinal Cord Dorsal Horn
Pain
Injections
Enzymes

Keywords

  • DON
  • Glutamate
  • Inflammatory pain
  • Primary afferents
  • c-fos

Cite this

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abstract = "In inflamed tissue, the levels of the excitatory amino acid glutamate are increased. Glutamate sensitizes peripheral axons of primary afferent neurons during inflammation leading to decreased firing threshold and hyperexcitability. One proposed source of glutamate is the primary afferent. Antagonizing glutamate receptors on peripheral axons of primary afferents during inflammation provides analgesia in animals and humans. The enzyme glutaminase is used by primary sensory neurons to convert glutamine to glutamate, and peripheral inhibition of glutaminase with 6-diazo-5-oxo-l-norleucine (DON) provides long-lasting analgesia during inflammation. In this study, we measured the effects of glutaminase inhibition on carrageenan-induced spinal Fos expression. Rats were given intraplantar injections of carrageenan and treated locally with either vehicle or DON. After 3 h of inflammation, hind paw swelling and spinal expression of Fos were examined. CellProfiler was used to automate Fos nuclei counting in five laminar groupings in the spinal cord (I-II, III-IV, V-VI, VII-IX, X). Carrageenan increased hind paw thickness by ∼70{\%} and spinal Fos expression in superficial (I-II) and deep (V-VI) laminae by 10-fold and 5-fold, respectively. Treatment with DON reduced hind paw swelling by ∼13{\%} and suppressed Fos expression in the laminae I-II by ∼54{\%}, but not the deep laminae. Our results further support the notion of glutamate as a peripheral inflammatory mediator and indicate that glutaminase should be considered as a novel therapeutic target for treatment of inflammatory pain.",
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Peripheral inhibition of glutaminase reduces carrageenan-induced Fos expression in the superficial dorsal horn of the rat. / Hoffman, Ernest M.; Miller, Kenneth.

In: Neuroscience Letters, Vol. 472, No. 3, 26.03.2010, p. 157-160.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peripheral inhibition of glutaminase reduces carrageenan-induced Fos expression in the superficial dorsal horn of the rat

AU - Hoffman, Ernest M.

AU - Miller, Kenneth

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