Journal article
Changes in the Disposition of Substance P in the Rostral Ventromedial Medulla after Inflammatory Injury in the Rat
Neuroscience, Vol.317, pp.1-11
03/11/2016
DOI: 10.1016/j.neuroscience.2015.12.054
PMCID: PMC4738059
PMID: 26762802
Abstract
This study examined whether peripheral inflammatory injury increases the levels or changes the disposition of substance P (SubP) in the rostral ventromedial medulla (RVM), which serves as a central relay in bulbospinal pathways of pain modulation. Enzyme immunoassay and reverse transcriptase quantitative polymerase chain reaction were used to measure SubP protein and transcript, respectively, in tissue homogenates prepared from the RVM and the periaqueductal gray and cuneiform nuclei of rats that had received an intraplantar injection of saline or complete Freund's adjuvant (CFA). Matrix Assisted Laser Desorption/Ionization Time of Flight analysis confirmed that the RVM does not contain hemokinin-1, which can confound measurements of SubP because it is recognized equally well by commercial antibodies for SubP. Levels of SubP protein in the RVM were unchanged four hours, four days and two weeks after injection of CFA.
Tac1
transcripts were similarly unchanged in the RVM four days or two weeks after CFA. In contrast, the density of SubP immunoreactive processes in the RVM increased 2-fold within four hours and 2.7-fold four days after CFA injection; it was unchanged at two weeks. SubP-immunoreactive processes in the RVM include axon terminals of neurons located in the periaqueductal gray and cuneiform nucleus. Substance P content in homogenates of the periaqueductal gray and cuneiform nucleus was significantly increased four days after CFA, but not at four hours or two weeks.
Tac1
transcripts in homogenates of these nuclei were unchanged four days and two weeks after CFA. These findings suggest that there is an increased mobilization of SubP within processes in the RVM shortly after injury accompanied by an increased synthesis of SubP in neurons that project to the RVM. These findings are consonant with the hypothesis that an increase in SubP release in the RVM contributes to the hyperalgesia that develops after peripheral inflammatory injury.
Details
- Title: Subtitle
- Changes in the Disposition of Substance P in the Rostral Ventromedial Medulla after Inflammatory Injury in the Rat
- Creators
- Uche P Maduka - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Marta V Hamity - Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Roxanne Y Walder - Department of Anesthesia, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Stephanie R White - University of IowaYalan Li - Department of Proteomics Core Facility, Carver College of Medicine, University of Iowa, Iowa City, IA 52242Donna L Hammond - Department of Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Neuroscience, Vol.317, pp.1-11
- DOI
- 10.1016/j.neuroscience.2015.12.054
- PMID
- 26762802
- PMCID
- PMC4738059
- NLM abbreviation
- Neuroscience
- ISSN
- 0306-4522
- eISSN
- 1873-7544
- Publisher
- Elsevier BV
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: F31NS073250, R01DA023576
- Language
- English
- Date published
- 03/11/2016
- Academic Unit
- Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984007158502771
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