INT125190

Context Info Confidence 0.62 First Reported 2005 Last Reported 2010 Negated 3 Speculated 9 Reported most in Body Documents 38 Total Number 47 Disease Relevance 32.57 Pain Relevance 23.20

cytosol (Trpv1) transport (Trpv1) plasma membrane (Trpv1) transmembrane transport (Trpv1) lipid metabolic process (Trpv1)

Anatomy Link Frequency neurons 12 skin 4 sensory neurons 4 body 3 bladder 3 Trpv1 (Mus musculus)

Pain Link Frequency Relevance Heat dorsal root ganglion 889 100.00 Pain 695 100.00 qutenza 565 100.00 agonist 67 100.00 substance P 55 100.00 Inflammation 386 99.84 diabetic neuropathy 229 99.84 spinal dorsal horn 39 99.84 antagonist 62 99.80 Nerve growth factor 143 99.62

Disease Link Frequency Relevance Heat Ganglion Cysts 1376 100.00 Targeted Disruption 641 100.00 Pain 636 100.00 Body Weight 146 100.00 Stress Incontinence 7 100.00 Diabetes Mellitus 1544 99.88 Disease 106 99.88 INFLAMMATION 422 99.84 Peripheral Neuropathy 227 99.84 Neuropathic Pain 390 99.52

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

We summarize disease-related changes in TRPV1 expression and its implications for therapy and potential adverse effects.

Regulation (changes) of Gene_expression (expression) of TRPV1 associated with disease

1) Confidence 0.62 Published 2008 Journal Clin J Pain Section Abstract Doc Link 18209521 Disease Relevance 0.27 Pain Relevance 0.47

These findings demonstrate that altered TRPV1 expression and function contribute to diabetes-induced changes in thermal perception.

Regulation (altered) of Gene_expression (expression) of TRPV1 associated with diabetes mellitus

2) Confidence 0.62 Published 2008 Journal Mol Pain Section Abstract Doc Link PMC2275252 Disease Relevance 1.60 Pain Relevance 0.61

There was no change in the number of neurons expressing TRPV1 in hypoalgesic mice relative to controls.

Neg (no) Regulation (change) of Gene_expression (expressing) of TRPV1 in neurons

3) Confidence 0.62 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 0.92 Pain Relevance 0.15

To determine whether cisplatin and oxaliplatin induced changes in TRPV1 protein expression, immunostaining of TRPV1 protein was performed in the TG of wild-type mice after a 3-week platinum drug treatment protocol [48].

Spec (whether) Regulation (changes) of Gene_expression (expression) of TRPV1 protein associated with trigeminal ganglion

4) Confidence 0.61 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.87 Pain Relevance 0.37

Changes in blood glucose level, body weight and thermal pain sensitivity in TRPV1 knock-out mice injected with STZ

Regulation (sensitivity) of Gene_expression (knock) of TRPV1 in body associated with targeted disruption, pain and body weight

5) Confidence 0.45 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 1.40 Pain Relevance 0.52

Changes in blood glucose level, body weight and thermal pain sensitivity in TRPV1 knock-out mice injected with STZ

Regulation (Changes) of in blood Gene_expression (knock) of TRPV1 in body associated with targeted disruption, pain and body weight

6) Confidence 0.45 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 1.48 Pain Relevance 0.53

Since TRPV1 is involved in inflammatory thermal sensation, it is logical to determine the expression and function of TRPV1 in DPN.

Spec (determine) Regulation (determine) of Spec (determine) Gene_expression (expression) of TRPV1 associated with inflammation and diabetic neuropathy

7) Confidence 0.45 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 1.42 Pain Relevance 1.06

Consequences of enhanced and reduced TRPV1 expression and function other than abnormal thermal sensation

Regulation (Consequences) of Gene_expression (expression) of TRPV1

8) Confidence 0.45 Published 2008 Journal Mol Pain Section Body Doc Link PMC2275252 Disease Relevance 0.95 Pain Relevance 0.28

Together, these results suggest the possibilities that TRPV1 channels in the bladder and urethra are involved in the sex difference in the LUT response to acid irritation and that these participate, e.g., via "cross talk" between the bladder and urethra, in the fine-tuning of intravesical pressure (or bladder emptying) at the bladder contraction phase under irritated LUT conditions but not in sensing for bladder filling during the storage period, although the contribution of the mechanism may be small.

Regulation (involved) of Gene_expression (channels) of TRPV1 in bladder associated with stress incontinence

9) Confidence 0.45 Published 2010 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 20237234 Disease Relevance 0.34 Pain Relevance 0

For example, it has been shown that TRPV1 sensitivity can be significantly modulated by many of the components of the inflammatory milieu (e.g. bradykinin, and NGF) present in inflamed skin as well as by local decreases in pH [2,52-54], that in turn could result in local peptide release in the inflamed tissue contributing to neurogenic inflammation [3].

Regulation (modulated) of Gene_expression (sensitivity) of TRPV1 in skin associated with inflammation, neurogenic inflammation and bradykinin

10) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2949725 Disease Relevance 1.22 Pain Relevance 0.46

In this study, we used models of cisplatin and oxaliplatin-induced neuropathy to investigate whether TRPV1, TRPM8, and TRPA1 mRNA expression were altered along with changes in thermal sensitivity observed in chemotherapeutic neuropathy.

Spec (whether) Regulation (altered) of Gene_expression (expression) of TRPV1 associated with induced neuropathy and neuropathic pain

11) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 1.16 Pain Relevance 0.70

Thus, in this pain model, cisplatin treatment did not result in an overall change in the proportion of TRPV1 immunoreactive TG neurons.

Regulation (change) of Gene_expression (proportion) of TRPV1 in neurons associated with pain and trigeminal ganglion

12) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.94 Pain Relevance 0.63

To characterize the population of TRPV1-protein positive neurons, we measured cell soma diameters in TRPV1-immunoreactive TG cells and observed average values of 16.66 ± 3.59 ?

Regulation (population) of Gene_expression (neurons) of TRPV1-protein in neurons associated with trigeminal ganglion

13) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.74 Pain Relevance 0.45

To determine whether the neurotoxic effects on the peripheral nervous system from platinum drug exposure induces changes in the expression of TRPV1, TRPM8, and TRPA1 mRNA, we used a previously described cell culture model [50].

Spec (whether) Regulation (changes) of Gene_expression (expression) of TRPV1 in peripheral nervous system associated with peripheral nervous system

14) Confidence 0.45 Published 2010 Journal Mol Pain Section Body Doc Link PMC2848188 Disease Relevance 0.92 Pain Relevance 0.56

In these experiments we assessed the effect of capsaicin treatment on the expression of NAPE-PLD and TRPV1 relative to the expression of GAPDH.

Regulation (effect) of Gene_expression (expression) of TRPV1 associated with qutenza

15) Confidence 0.45 Published 2009 Journal Neuroscience Section Body Doc Link PMC2724038 Disease Relevance 0 Pain Relevance 0.10

However, assuming that the TRPV1 mRNA we detected in our cultures following the capsaicin treatment, was expressed in neurons, which, in spite of their TRPV1 expression, were not responsive to capsaicin, or alternatively, they were responsive to capsaicin but resistant to the subsequent excitotoxicity, it is tempting to propose that TRPV1 and NAPE-PLD could be co-expressed to a high degree, in primary sensory neurons.

Neg (not) Regulation (responsive) of Gene_expression (expression) of TRPV1 in primary sensory neurons associated with qutenza

16) Confidence 0.45 Published 2009 Journal Neuroscience Section Body Doc Link PMC2724038 Disease Relevance 0 Pain Relevance 0.68

In these experiments we assessed the effect of capsaicin treatment on the expression of NAPE-PLD and TRPV1 relative to the expression of GAPDH.

Regulation (relative) of Gene_expression (expression) of TRPV1 associated with qutenza

17) Confidence 0.45 Published 2009 Journal Neuroscience Section Body Doc Link PMC2724038 Disease Relevance 0 Pain Relevance 0.10

This study used real-time PCR to quantitatively track changes in TRPV1-4 mRNA expression in the spiral, vestibular, and trigeminal ganglia and the kidney from kanamycin (KM)-treated mice.

Regulation (changes) of Gene_expression (expression) of TRPV1 in kidney

18) Confidence 0.45 Published 2005 Journal Hear. Res. Section Abstract Doc Link 15721568 Disease Relevance 0.06 Pain Relevance 0.23

increases TRPV1 expression through TNF-?

Regulation (through) of Gene_expression (expression) of TRPV1

19) Confidence 0.44 Published 2009 Journal Mol Pain Section Body Doc Link PMC2706230 Disease Relevance 0.96 Pain Relevance 0.60

Therefore, we examined whether a similar signal transduction pathway is involved in the regulation of TRPV1 responses through EP1.

Spec (whether) Regulation (regulation) of Gene_expression (responses) of TRPV1

20) Confidence 0.44 Published 2005 Journal Mol Pain Section Body Doc Link PMC1074353 Disease Relevance 0 Pain Relevance 0.11

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