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Long-term reversal of chronic pain behavior in rodents through elevation of spinal agmatine.
Peterson, Cristina D; Waataja, Jonathan J; Kitto, Kelley F; Erb, Samuel J; Verma, Harsha; Schuster, Daniel J; Churchill, Caroline C; Riedl, Maureen S; Belur, Lalitha R; Wolf, Daniel A; McIvor, R Scott; Vulchanova, Lucy; Wilcox, George L; Fairbanks, Carolyn A.
Afiliação
  • Peterson CD; Department of Pharmaceutics, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA; Department of Experimental and Clinic
  • Waataja JJ; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
  • Kitto KF; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
  • Erb SJ; Department of Pharmaceutics, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA.
  • Verma H; Department of Pharmaceutics, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA.
  • Schuster DJ; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
  • Churchill CC; Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA.
  • Riedl MS; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
  • Belur LR; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA.
  • Wolf DA; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA.
  • McIvor RS; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA.
  • Vulchanova L; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA.
  • Wilcox GL; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA; Department of Pharmacology, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA; Department of Dermatology, University
  • Fairbanks CA; Department of Pharmaceutics, University of Minnesota, Minneapolis, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, College of Pharmacy, 9-177 Weaver Densford Hall, 308 Harvard Street S.E., Minneapolis, MN 55455, USA; Department of Experimental and Clinic
Mol Ther ; 31(4): 1123-1135, 2023 04 05.
Article em En | MEDLINE | ID: mdl-36710491
ABSTRACT
Chronic pain remains a significant burden worldwide, and treatments are often limited by safety or efficacy. The decarboxylated form of L-arginine, agmatine, antagonizes N-methyl-d-aspartate receptors, inhibits nitric oxide synthase, and reverses behavioral neuroplasticity. We hypothesized that expressing the proposed synthetic enzyme for agmatine in the sensory pathway could reduce chronic pain without motor deficits. Intrathecal delivery of an adeno-associated viral (AAV) vector carrying the gene for arginine decarboxylase (ADC) prevented the development of chronic neuropathic pain as induced by spared nerve injury in mice and rats and persistently reversed established hypersensitivity 266 days post-injury. Spinal long-term potentiation was inhibited by both exogenous agmatine and AAV-human ADC (hADC) vector pre-treatment but was enhanced in rats treated with anti-agmatine immunoneutralizing antibodies. These data suggest that endogenous agmatine modulates the neuroplasticity associated with chronic pain. Development of approaches to access this inhibitory control of neuroplasticity associated with chronic pain may yield important non-opioid pain-relieving options.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Agmatina / Dor Crônica Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Agmatina / Dor Crônica Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article