INT14556

Context Info Confidence 0.69 First Reported 1990 Last Reported 2010 Negated 3 Speculated 5 Reported most in Abstract Documents 105 Total Number 111 Disease Relevance 52.21 Pain Relevance 24.04

extracellular space (Igf1) extracellular region (Igf1)

Anatomy Link Frequency Plasma 6 brain structure 5 sensory neurons 5 liver 5 muscle 5 Igf1 (Mus musculus)

Pain Link Frequency Relevance Heat Calcitonin gene-related peptide 152 100.00 opiate 2 100.00 qutenza 140 99.98 narcan 10 99.98 tolerance 109 99.78 Somatostatin 357 99.76 Osteoarthritis 7 99.74 fluoxetine 19 99.72 Demyelination 34 99.28 Central nervous system 30 99.16

Disease Link Frequency Relevance Heat Apoptosis 363 100.00 Injury 147 100.00 Pituitary Cancer 67 99.84 Impaired Glucose Tolerance 83 99.78 Hematological Disease 40 99.78 Osteoarthritis 6 99.74 Hypertrophy 46 99.66 Obesity 164 99.64 Targeted Disruption 268 99.62 Prostate Cancer 45 99.50

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

RESULTS: Subcutaneous administration of capsaicin significantly increased dermal IGF-I levels at 30 min after administration in WT mice (p < 0.01), but not in CGRP-knockout mice.

Positive_regulation (increased) of IGF-I

1) Confidence 0.69 Published 2007 Journal Growth Horm. IGF Res. Section Body Doc Link 17569567 Disease Relevance 0.16 Pain Relevance 0

A further increase in serum IGF-1 levels with gene therapy also improved motor function, consistent with the observed prevention of both muscle atrophy and peripheral motor nerve fiber demyelination.

Positive_regulation (increase) of IGF-1 in muscle associated with demyelination and muscular atrophy

2) Confidence 0.69 Published 2008 Journal Mol. Ther. Section Abstract Doc Link 18545223 Disease Relevance 1.21 Pain Relevance 0.80

We investigated whether increasing systemic IGF-1 could improve neuronal function in hyper- and hypoalgesic STZ-treated mice.

Positive_regulation (increasing) of IGF-1 in neuronal

3) Confidence 0.69 Published 2008 Journal Mol. Ther. Section Abstract Doc Link 18545223 Disease Relevance 1.06 Pain Relevance 0.73

Administration of capsaicin increased tissue levels of IGF-I and IGF-I mRNA in various organs in wild-type (WT) mice, but not in CGRP-knock-out (CGRP-/-) mice.

Positive_regulation (increased) of IGF-I associated with targeted disruption, qutenza and calcitonin gene-related peptide

4) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17360009 Disease Relevance 0.51 Pain Relevance 0.70

Administration of CGRP increased tissue levels of IGF-I and IGF-I mRNA in both WT and CGRP-/- mice.

Positive_regulation (increased) of IGF-I associated with calcitonin gene-related peptide

5) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17360009 Disease Relevance 0.58 Pain Relevance 0.78

Administration of CGRP increased tissue levels of IGF-I and IGF-I mRNA in both WT and CGRP-/- mice.

Positive_regulation (increased) of IGF-I associated with calcitonin gene-related peptide

6) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17360009 Disease Relevance 0.58 Pain Relevance 0.78

Administration of capsaicin increased tissue levels of IGF-I and IGF-I mRNA in various organs in wild-type (WT) mice, but not in CGRP-knock-out (CGRP-/-) mice.

Positive_regulation (increased) of IGF-I associated with targeted disruption, qutenza and calcitonin gene-related peptide

7) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17360009 Disease Relevance 0.51 Pain Relevance 0.69

Although administration of capsaicin enhanced increases in IGF-I levels and reduced reperfusion-induced events in WT mice, it had no effect in CGRP-/- mice.

Positive_regulation (increases) of IGF-I associated with qutenza and calcitonin gene-related peptide

8) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Abstract Doc Link 17360009 Disease Relevance 0.56 Pain Relevance 0.90

Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I, thereby reducing reperfusion-induced apoptosis in mice.

Positive_regulation (increases) of IGF-I in sensory neurons associated with qutenza and apoptosis

9) Confidence 0.69 Published 2007 Journal Neuropharmacology Section Title Doc Link 17360009 Disease Relevance 0.48 Pain Relevance 0.82

Topical application of GG increased dermal levels of IGF-I, IGF-I mRNA, and collagen in wild-type mice, but not in CGRP-knockout mice.

Neg (not) Positive_regulation (increased) of IGF-I associated with targeted disruption

10) Confidence 0.69 Published 2010 Journal Biosci. Biotechnol. Biochem. Section Abstract Doc Link 20378988 Disease Relevance 0.38 Pain Relevance 0.21

Topical application of GG increased dermal levels of IGF-I, IGF-I mRNA, and collagen in wild-type mice, but not in CGRP-knockout mice.

Neg (not) Positive_regulation (increased) of IGF-I associated with targeted disruption

11) Confidence 0.69 Published 2010 Journal Biosci. Biotechnol. Biochem. Section Abstract Doc Link 20378988 Disease Relevance 0.38 Pain Relevance 0.21

Significant increases of the hippocampal tissue levels of CGRP, IGF-I, and IGF-I messenger RNA (mRNA) were observed after capsaicin administration in WT mice (P < 0.01) but not in CGRP-/- mice.

Positive_regulation (increases) of IGF-I associated with qutenza and calcitonin gene-related peptide

12) Confidence 0.69 Published 2009 Journal Transl Res Section Abstract Doc Link 19595440 Disease Relevance 0.52 Pain Relevance 1.07

Significant increases of the hippocampal tissue levels of CGRP, IGF-I, and IGF-I messenger RNA (mRNA) were observed after capsaicin administration in WT mice (P < 0.01) but not in CGRP-/- mice.

Positive_regulation (increases) of IGF-I associated with qutenza and calcitonin gene-related peptide

13) Confidence 0.69 Published 2009 Journal Transl Res Section Abstract Doc Link 19595440 Disease Relevance 0.52 Pain Relevance 1.07

These observations suggest that topical application of capsaicin and related compounds might be useful in the treatment of detrimental morphological changes of the skin in patients with growth hormone deficiency and those in the elderly by increasing dermal IGF-I levels.

Positive_regulation (increasing) of IGF-I in skin associated with qutenza and growth hormone deficiency

14) Confidence 0.68 Published 2007 Journal Growth Horm. IGF Res. Section Abstract Doc Link 17307377 Disease Relevance 0.10 Pain Relevance 0.55

Topical application of 0.01% capsaicin significantly increased dermal IGF-I levels from 30 to 180min (p<0.01), but not at 360min, after application in mice.

Positive_regulation (increased) of IGF-I associated with qutenza

15) Confidence 0.68 Published 2007 Journal Growth Horm. IGF Res. Section Abstract Doc Link 17307377 Disease Relevance 0 Pain Relevance 0.73

In the present study, we attempted to determine whether topical application of capsaicin and related compounds increases dermal IGF-I level in mice and whether it increases facial skin elasticity in humans.

Spec (whether) Positive_regulation (increases) of IGF-I in skin associated with qutenza

16) Confidence 0.68 Published 2007 Journal Growth Horm. IGF Res. Section Abstract Doc Link 17307377 Disease Relevance 0 Pain Relevance 0.72

Topical application of 0.01% capsaicinoids (dihydrocapsaicin and nordihydrocapsaicin), 0.01% capsinoids (capsiate, dihydrocapsiate and nordihydrocapsiate), 0.01% anandamide (an endogenous agonist of VR-1), and 0.01% nonylic acid vanillylamide (a synthetic capsaicin) significantly increased dermal IGF-I levels at 30min after topical application in mice (p<0.01).

Positive_regulation (increased) of IGF-I associated with qutenza and agonist

17) Confidence 0.68 Published 2007 Journal Growth Horm. IGF Res. Section Abstract Doc Link 17307377 Disease Relevance 0 Pain Relevance 0.79

Stimulation of sensory neurons by capsaicin increases tissue levels of IGF-I and IGF-I mRNA in various organs via increased calcitonin gene-related peptide (CGRP) release in mice.

Positive_regulation (increases) of IGF-I in sensory neurons associated with qutenza and calcitonin gene-related peptide

18) Confidence 0.68 Published 2008 Journal Curr. Med. Chem. Section Abstract Doc Link 19075656 Disease Relevance 0.37 Pain Relevance 0.36

Since administration of GH or IGF-I has some deleterious effects, pharmacological stimulation of sensory neurons leading to increased tissue IGF-I levels might be a novel therapeutic strategy for various pathologic conditions.

Positive_regulation (increased) of IGF-I in sensory neurons

19) Confidence 0.68 Published 2008 Journal Curr. Med. Chem. Section Abstract Doc Link 19075656 Disease Relevance 0.61 Pain Relevance 0.45

Topical application of capsaicin increases dermal levels of IGF-I by stimulating sensory neurons in mice and increases facial skin elasticity in humans.

Positive_regulation (increases) of IGF-I in sensory neurons associated with qutenza

20) Confidence 0.68 Published 2008 Journal Curr. Med. Chem. Section Abstract Doc Link 19075656 Disease Relevance 0.75 Pain Relevance 0.55

General Comments

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