INT48593

Context Info Confidence 0.68 First Reported 1994 Last Reported 2010 Negated 16 Speculated 16 Reported most in Body Documents 420 Total Number 436 Disease Relevance 226.15 Pain Relevance 114.71

cytosol (NOS1) oxidoreductase activity (NOS1) cytoskeleton (NOS1) cytoplasm (NOS1)

Anatomy Link Frequency neuronal 30 brain 18 lung 10 nerve 9 macrophages 9 NOS1 (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 3166 100.00 cytokine 1636 100.00 Pain 747 100.00 nMDA receptor 680 100.00 Spinal cord 524 100.00 antagonist 394 100.00 dorsal root ganglion 201 100.00 Opioid 163 100.00 Eae 112 100.00 metalloproteinase 88 100.00

Disease Link Frequency Relevance Heat INFLAMMATION 3654 100.00 Nervous System Injury 358 100.00 Ganglion Cysts 244 100.00 Appetite Loss 127 100.00 Temporomandibular Joint Syndrome 6 100.00 Stress 2937 99.98 Pain 824 99.96 Increased Venous Pressure Under Development 1012 99.92 Urological Neuroanatomy 132 99.88 Neurodegenerative Disease 266 99.84

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Therapeutic stimulation of penile nitric oxide synthase (NOS) and related pathways.

Positive_regulation (stimulation) of NOS

1) Confidence 0.68 Published 2000 Journal Drugs Today Section Title Doc Link 12879114 Disease Relevance 0.51 Pain Relevance 0.09

The increased NOS immunoreactivities could be antagonized by pre-treatment with sumatriptan.

Positive_regulation (increased) of NOS associated with sumatriptan

2) Confidence 0.59 Published 2008 Journal J Headache Pain Section Abstract Doc Link 18688693 Disease Relevance 0.31 Pain Relevance 0.46

N(2)O stimulates NOS enzyme activity in C57BL/6 but not DBA/2 mice.

Positive_regulation (stimulates) of NOS associated with nociceptor

3) Confidence 0.59 Published 2003 Journal Brain Res. Section Title Doc Link 12763262 Disease Relevance 0.08 Pain Relevance 0.28

Therapeutic stimulation of penile nitric oxide synthase (NOS) and related pathways.

Positive_regulation (stimulation) of nitric oxide synthase

4) Confidence 0.59 Published 2000 Journal Drugs Today Section Title Doc Link 12879114 Disease Relevance 0.51 Pain Relevance 0.09

There are three NOS isoforms, endothelial cell NOS (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS).

Positive_regulation (inducible) of NOS in neuronal

5) Confidence 0.58 Published 2004 Journal J Int Soc Sports Nutr Section Body Doc Link PMC2129157 Disease Relevance 0 Pain Relevance 0

The activation of neuronal NO synthase (nNOS) and other Ca2+ -dependant enzymes may account for many of the beneficial as well as deleterious affects associated with NMDA receptor activation, including neuronal development (Garthwaite 1991), learning, and memory (Iga et al 1993), but also cell death and neurodegeneration (Dawson VL and Dawson TM 1995).

Positive_regulation (activation) of nNOS in neuronal associated with nmda receptor and death

6) Confidence 0.56 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.69 Pain Relevance 0.43

The activation of neuronal NO synthase (nNOS) and other Ca2+ -dependant enzymes may account for many of the beneficial as well as deleterious affects associated with NMDA receptor activation, including neuronal development (Garthwaite 1991), learning, and memory (Iga et al 1993), but also cell death and neurodegeneration (Dawson VL and Dawson TM 1995).

Positive_regulation (activation) of neuronal NO synthase in neuronal associated with nmda receptor and death

7) Confidence 0.56 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.69 Pain Relevance 0.43

Inducible NOS like immunoreactivity was detected in decidualised stromal cells and also expressed in tissues from first trimester of pregnancy.

Positive_regulation (Inducible) of NOS in stromal cells

8) Confidence 0.53 Published 2005 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1215514 Disease Relevance 0.27 Pain Relevance 0

Inducible NOS isoform is elevated in tissues of patients with endometriosis [131].

Positive_regulation (Inducible) of NOS associated with endometriosis

9) Confidence 0.53 Published 2005 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1215514 Disease Relevance 1.24 Pain Relevance 0.64

Expression of inducible NOS was highest in patients with preterm pregnancy and not in patients in term labor.

Positive_regulation (inducible) of NOS

10) Confidence 0.53 Published 2005 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1215514 Disease Relevance 0.19 Pain Relevance 0

Significant increase in the levels of serum metabolites of NOS amongst users of progestin only contraceptives has been reported [120].

Positive_regulation (increase) of NOS

11) Confidence 0.53 Published 2005 Journal Reprod Biol Endocrinol Section Body Doc Link PMC1215514 Disease Relevance 0.17 Pain Relevance 0

The types of NOS are classified as endothelial NOS (eNOS; NOS3), which regulates vascular function; inducible NOS (iNOS; NOS2), which is present in vasculature but is also involved in immune responses; and neuronal NOS (nNOS; NOS1), which is present predominantly in the peripheral and central nervous systems. eNOS and nNOS are the constitutive forms of NOS.

Positive_regulation (inducible) of NOS in central nervous systems

12) Confidence 0.51 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2582806 Disease Relevance 0.54 Pain Relevance 0.20

NOS phosphorylation in some other brain regions, which may be regulated by PKA, probably contributes to the increase of NOS activity in morphine-dependent mice.

Positive_regulation (increase) of NOS in brain associated with morphine

13) Confidence 0.51 Published 1999 Journal Sheng Li Xue Bao Section Abstract Doc Link 11499006 Disease Relevance 0.14 Pain Relevance 1.09

Although the presence of neuronal nitric oxide synthase (nNOS) has been demonstrated in human clitoral corpus cavernosum, functional evidence for the nitrergic neurotransmission as a nonadrenergic noncholinergic (NANC) transmitter has been limited to animal studies.

Positive_regulation (presence) of nNOS in neuronal associated with neuronal nitric oxide synthase

14) Confidence 0.50 Published 2004 Journal Int. J. Impot. Res. Section Abstract Doc Link 14961056 Disease Relevance 0 Pain Relevance 0.11

The activity of the constitutive NOS depends on Ca2+ and calmodulin, whereas the inducible NOS is independent of Ca2+.

Positive_regulation (inducible) of NOS

15) Confidence 0.49 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.18 Pain Relevance 0.15

Thus, while an initial activation of constitutive NOS may follow acute stress (De Oliveira et al 2000), iNOS appears to play a more prominent role during chronic stress (Homayoun et al 2002).

Positive_regulation (activation) of constitutive NOS associated with stress

16) Confidence 0.49 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.96 Pain Relevance 0.15

This suggests that overproduction of NO in the hippocampus following TDS stress more likely is the result of iNOS induction and not activation of nNOS.

Neg (not) Positive_regulation (activation) of nNOS in hippocampus associated with stress and hippocampus

17) Confidence 0.49 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.85 Pain Relevance 0.28

Indeed, activation of NOS by TDS stress is selectively blocked by the selective iNOS inhibitor, aminoguanidine and not the selective nNOS inhibitor, 7-nitroindazole (Harvey et al 2004).

Positive_regulation (activation) of NOS associated with stress

18) Confidence 0.49 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.86 Pain Relevance 0.28

An interesting observation was the ability of KCZ to increase the dissociation constant (Km) of hippocampal NOS.

Positive_regulation (increase) of NOS

19) Confidence 0.49 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2413191 Disease Relevance 0.55 Pain Relevance 0.08

In this work, we examined physiological and morphological evidence for nitric oxide synthase (NOS) activation in the chronic constriction injury model of neuropathic pain in rats.

Spec (examined) Positive_regulation (activation) of NOS associated with eae, injury and neuropathic pain

20) Confidence 0.48 Published 1998 Journal Eur. J. Neurosci. Section Abstract Doc Link 9751155 Disease Relevance 0.92 Pain Relevance 0.56

General Comments

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