Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity

@article{DMello2015DimethylarginineD1,
  title={Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity},
  author={Richard D'Mello and Claire A. Sand and Sophie Pezet and James Leiper and Egle Gaurilcikaite and Stephen B. McMahon and Anthony Henry Dickenson and Manasi Nandi},
  journal={Pain},
  year={2015},
  volume={156},
  pages={2052 - 2060}
}
Abstract Activation of neuronal nitric oxide synthase, and consequent production of nitric oxide (NO), contributes to spinal hyperexcitability and enhanced pain sensation. All NOS isoforms are inhibited endogenously by asymmetric dimethylarginine, which itself is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). Inhibition of DDAH can indirectly attenuate NO production by elevating asymmetric dimethylarginine concentrations. Here, we show that the DDAH-1 isoform is constitutively… 
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References

SHOWING 1-10 OF 38 REFERENCES
Neuronal Nitric Oxide Synthase Modulation of Dorsal Horn Neuronal Responses in the Rat: A Developmental Study
Nitric oxide (NO) is a diffusible chemical messenger functionally linked to N-methyl-D-aspartate (NMDA) receptor activity and has been shown to be involved in modulating numerous pathways in the
Asymmetric dimethylarginine (ADMA)--a modulator of nociception in opiate tolerance and addiction?
Induction of spinal cord neuronal nitric oxide synthase (NOS) after formalin injection in the rat hind paw
Genetic and Pharmacological Inhibition of Dimethylarginine Dimethylaminohydrolase 1 Is Protective in Endotoxic Shock
TLDR
Pharmacological and genetic reduction of DDAH1 activity is protective against the vascular changes observed during endotoxic shock.
Perturbing PSD-95 Interactions With NR2B-subtype Receptors Attenuates Spinal Nociceptive Plasticity and Neuropathic Pain
Peripheral inflammation or nerve injury induces a primary afferent barrage into the spinal cord, which can cause N-methyl -aspartate (NMDA) receptor-dependent alterations in the responses of dorsal
Disruption of methylarginine metabolism impairs vascular homeostasis
TLDR
It is shown that loss of DDAH-1 activity leads to accumulation of ADMA and reduction in NO signaling, which causes vascular pathophysiology, including endothelial dysfunction, increased systemic vascular resistance and elevated systemic and pulmonary blood pressure, and it is suggested that DDAh inhibition could be harnessed therapeutically to reduce the vascular collapse associated with sepsis.
Dimethylarginine dimethylaminohydrolase (DDAH) as a nerve‐injury‐associated molecule: mRNA localization in the rat brain and its coincident up‐regulation with neuronal NO synthase (nNOS) in axotomized motoneurons
TLDR
It is demonstrated that both DDAH and nNOS mRNAs are up‐regulated after axotomy in injured hypoglossal motor neurons, and speculated that both genes are involved in the upregulation of NO production following nerve transection, although the role of NO in the process of nerve regeneration is so far unknown.
Genetic knockout and pharmacologic inhibition of neuronal nitric oxide synthase attenuate nerve injury-induced mechanical hypersensitivity in mice
TLDR
The findings suggest that nNOS, especially in the dorsal root ganglion, may participate in the development and/or maintenance of mechanical hypersensitivity after nerve injury.
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