INT103251

Context Info Confidence 0.43 First Reported 2002 Last Reported 2010 Negated 1 Speculated 0 Reported most in Body Documents 13 Total Number 13 Disease Relevance 9.36 Pain Relevance 8.86

extracellular space (Calca) extracellular region (Calca) nucleus (Calca) intracellular (Calca) cytoplasm (Calca)

Anatomy Link Frequency neuronal 4 neurons 4 blood 2 cardiovascular system 2 skin 2 Calca (Mus musculus)

Pain Link Frequency Relevance Heat Pain 209 100.00 qutenza 191 100.00 substance P 35 100.00 calcitonin gene related peptide 28 100.00 bradykinin 25 100.00 Calcitonin gene-related peptide 25 100.00 Neurotransmitter 20 100.00 Glutamate 7 100.00 dorsal root ganglion 87 99.76 Sumatriptan 1 99.50

Disease Link Frequency Relevance Heat Pain 229 100.00 Nociception 94 100.00 Ganglion Cysts 91 99.76 Diabetes Mellitus 261 99.48 Increased Venous Pressure Under Development 24 98.72 Amputation 3 96.80 Muscular Spasm 4 96.64 Compartment Syndromes 1 95.60 Coronary Artery Disease 8 94.72 Cv Unclassified Under Development 11 94.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Administration of ruthenium red (1 mg/kg(-1), i.p.), vanilloid receptor antagonist, and sumatriptan (50 mg/kg(-1), i.p.), a CGRP release inhibitor, attenuated diabetes and SHS induced decrease in nociceptive threshold and increase in serum nitrite oxide levels.

Negative_regulation (inhibitor) of Localization (release) of CGRP associated with nociception, sumatriptan, diabetes mellitus and antagonist

1) Confidence 0.43 Published 2008 Journal Yakugaku Zasshi Section Abstract Doc Link 18981706 Disease Relevance 1.45 Pain Relevance 0.84

The substantial increase of CGRP release evoked by noxious heat (47 degrees C) was diminished under muscarine by >50% in the WT and M4 KO animals but remained unaltered in the M2 KO mice.

Negative_regulation (diminished) of Localization (release) of CGRP associated with calcitonin gene-related peptide

2) Confidence 0.43 Published 2002 Journal J. Neurosci. Section Abstract Doc Link 12045234 Disease Relevance 0.37 Pain Relevance 0.55

Both L768242 and (+)-AM1241 dose dependently (EC50 of 3.6 and 4.5 nM, respectively) reduced capsaicin-induced calcitonin gene-related peptide (CGRP) release.

Negative_regulation (reduced) of Localization (release) of CGRP associated with qutenza and calcitonin gene-related peptide

3) Confidence 0.41 Published 2006 Journal Eur. J. Neurosci. Section Abstract Doc Link 16553616 Disease Relevance 0.25 Pain Relevance 0.95

Noxious heat-induced calcitonin gene-related peptide release showed clear deficits (<50%) in TRPV1 deficient skin, but the stimulated calcitonin gene-related peptide release from the isolated skull dura was unaffected.

Neg (unaffected) Negative_regulation (unaffected) of Localization (release) of calcitonin in skin associated with calcitonin gene-related peptide

4) Confidence 0.32 Published 2005 Journal Neuroscience Section Abstract Doc Link 16165301 Disease Relevance 0.07 Pain Relevance 0.55

The role of TRPV1 in the cardiovascular system has been addressed: 1) Infusion of TRPV1 agonists significantly alters blood pressure, which could be mostly reversed by selective TRPV1 antagonists [24,25]; 2) Ablation of TRPV1 expressing C fiber terminals by capsaicin or resiniferatoxin (RTX) results in the loss of CGRP release, increased plasma renin activity, and an inability to control salt loading by the kidneys [14]; 3) Activation of TRPV1 or ASIC3 by protons during ischemia mediates a sympathoexcitatory reflex that is abolished by RTX treatment [5,26].

Negative_regulation (loss) of Localization (release) of CGRP in cardiovascular system associated with c fibre, qutenza, ischemia, antagonist, agonist and calcitonin gene-related peptide

5) Confidence 0.20 Published 2006 Journal Mol Pain Section Body Doc Link PMC1563450 Disease Relevance 0.18 Pain Relevance 0.56

We propose that reduction of PG levels may contribute to deleterious vascular effects by decreasing sensitization of TRPV1 and subsequent reduction of CGRP and SP release.

Negative_regulation (reduction) of Localization (release) of CGRP associated with substance p and calcitonin gene-related peptide

6) Confidence 0.20 Published 2006 Journal Mol Pain Section Body Doc Link PMC1563450 Disease Relevance 0.38 Pain Relevance 0.62

Pretreatment with capsazepine, an inhibitor of vanilloid receptor-1 activation, and with KT5720, an inhibitor of protein kinase A, reversed GG-induced increases in CGRP release from DRG neurons.

Negative_regulation (reversed) of Localization (release) of CGRP in neurons associated with dorsal root ganglion

7) Confidence 0.19 Published 2010 Journal Biosci. Biotechnol. Biochem. Section Abstract Doc Link 20378988 Disease Relevance 0.37 Pain Relevance 0.22

TRPV1 mediated CGRP release could play a role in increasing blood supply to malignancies of the GI tract; the beneficial effect of COX inhibitors in this regard may arise from their ability to reduce TRPV1-mediated CGRP release and inhibition of PG-mediated angiogenesis.

Negative_regulation (reduce) of Localization (release) of CGRP in blood associated with calcitonin gene related peptide

8) Confidence 0.16 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2647151 Disease Relevance 0.61 Pain Relevance 0.89

If untreated, this might lead to more serious complications, which include changes in microvascular function due to decreased release of CGRP, neuronal loss, development of gangrene and total loss of sensation leading to amputation.

Negative_regulation (decreased) of Localization (release) of CGRP in neuronal associated with amputation and increased venous pressure under development

9) Confidence 0.14 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 1.22 Pain Relevance 0.31

This effect is TRPV1 specific as it was inhibited by capsazepine and suggested to occur as a result of CGRP and tachykinin release upon TRPV1 activation [86].

Negative_regulation (result) of Localization (release) of CGRP associated with calcitonin gene related peptide

10) Confidence 0.13 Published 2008 Journal Current Neuropharmacology Section Body Doc Link PMC2647151 Disease Relevance 0.64 Pain Relevance 0.58

If untreated, this might lead to more serious complications, which include changes in microvascular function due to decreased release of CGRP, neuronal loss, development of gangrene and total loss of sensation leading to amputation.

Negative_regulation (decreased) of Localization (release) of CGRP in neuronal associated with amputation and increased venous pressure under development

11) Confidence 0.10 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 1.22 Pain Relevance 0.31

In central sensitization, wide-range function neurons of the spinal cord erroneously perceive non-nociceptive input (such as that from muscle spindles) as nociceptive.39 In cell cultures and animal studies, BoNTA diminishes the release of pain neurotransmitters such as substance P, calcitonin gene-related peptide, and bradykinin.40

Negative_regulation (diminishes) of Localization (release) of calcitonin in neurons associated with nociception, pain, central sensitization, bradykinin, calcitonin gene-related peptide, spinal cord, neurotransmitter and substance p

12) Confidence 0.03 Published 2010 Journal Journal of pain research Section Body Doc Link PMC3004649 Disease Relevance 1.45 Pain Relevance 1.12

In diminishing synaptic acetylcholine, the co-release of local factors for nociceptive transmission, such as calcitonin-gene-related protein (CGRP), glutamate, substance P and bradykinin (Arezzo 2002), is reduced as well.

Negative_regulation (reduced) of Localization (release) of calcitonin-gene-related protein associated with nociception, glutamate, bradykinin and substance p

13) Confidence 0.03 Published 2007 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2656321 Disease Relevance 1.14 Pain Relevance 1.37

General Comments

This test has worked.